method for forming a tubular medical device

ABSTRACT

A method and process for at least partially forming a medical device that is at least partially formed of a metal alloy which improves the physical properties of the medical device.

The present invention claims priority on PCT Application Serial No.PCT/US08/86126 filed Dec. 10, 2008, which in turn claim priority on U.S.Provisional Application Ser. No. 61/008,332 filed Dec. 19, 2007, whichare fully incorporated herein by reference.

The present invention also claims priority on PCT Application Serial No.PCT/US08/86126 filed Dec. 10, 2008, which in turn claim priority on U.S.patent application Ser. No. 11/635,158 filed Dec. 1, 2006, which in turnis a continuation-in-part of U.S. patent application Ser. No. 11/343,104filed Jan. 30, 2006, which in turn is a continuation-in-part of U.S.Pat. application Ser. No. 11/282,461 filed Nov. 18, 2005 entitled “MetalAlloy for a Stent” which claims priority on U.S. Provisional ApplicationSer. No. 60/694,891 filed Jun. 29, 2005 entitled “Improved Metal Alloysfor Medical Devices,” all of which are incorporated herein by reference.

The present invention also claims priority on PCT Application Serial No.PCT/US08/86126 filed Dec. 10, 2008, which in turn claim priority on U.S.patent application Ser. No. 11/635,158 filed Dec. 1, 2006, which in turnis a continuation-in-part of U.S. patent application Ser. No. 11/343,104filed Jan. 30, 2006, which in turn is a continuation-in-part of U.S.patent application Ser. No. 11/282,376 filed Nov. 18, 2005 entitled“Metal Alloy for a Stent,” all of which are incorporated herein byreference.

The present invention also claims priority on PCT Application Serial No.PCT/US08/86126 filed Dec. 10, 2008, which in turn claim priority on U.S.patent application Ser. No. 11/635,158 filed Dec. 1, 2006, which in turnis a continuation-in-part of U.S. patent application Ser. No. 11/343,104filed Jan. 30, 2006, which in turn claims priority on U.S. ProvisionalApplication Ser. No. 60/658,226 filed Mar. 3, 2005 entitled “ImprovedMetal Alloys for Medical Devices”; 60/694,881 filed Jun. 29, 2005entitled “Improved Metal Alloys for Medical Devices”; and 60/739,688filed Nov. 23, 2005 entitled “Process for Forming an Improved MetalAlloy Stent,” all of which are incorporated herein by reference.

The present invention also claims priority on PCT Application Serial No.PCT/US08/86126 filed Dec. 10, 2008, which in turn claim priority on U.S.patent application Ser. No. 12/272,317 filed Nov. 17, 2008, which is acontinuation of Ser. No. 11/338,265 filed Jan. 24, 2006, which claimspriority on U.S. Provisional Application Ser. No. 60/658,226 filed Mar.3, 2005 entitled “Improved Metal Alloys for Medical Devices”; 60/694,881filed Jun. 29, 2005 entitled “Improved Metal Alloys for MedicalDevices”; and 60/739,688 filed Nov. 23, 2005 entitled “Process forForming an Improved Metal Alloy Stent”, all of which are incorporatedherein by reference.

The present invention also claims priority on PCT Application Serial No.PCT/US08/86126 filed Dec. 10, 2008, which in turn claim priority on U.S.patent application Ser. No. 11/363,967 filed Feb. 28, 2006, which inturn claims priority on U.S. Provisional Application Ser. No. 60/658,226filed Mar. 3, 2005 entitled “Improved Metal Alloys for Medical Devices”and 60/694,903 filed Jun. 29, 2005 entitled “Improved Metal Alloys forMedical Devices”, all of which are incorporated herein by reference.

The present invention also claims priority on PCT Application Serial No.PCT/US08/86126 filed Dec. 10, 2008, which in turn claim priority on PCTApplication Serial No. PCT/US2007/022862 filed Oct. 30, 2007, which inturn claims priority on U.S. patent application Ser. No. 11/363,967filed Feb. 28, 2006, which in turn claims priority on U.S. ProvisionalApplication Ser. No. 60/658,226 filed Mar. 3, 2005 entitled “ImprovedMetal Alloys for Medical Devices” and 60/694,903 filed Jun. 29, 2005entitled “Improved Metal Alloys for Medical Devices”, all of which areincorporated herein by reference.

The invention relates generally to medical devices, and particularly toa method and process for forming a medical device that is at leastpartially formed of a novel metal alloy, and more particularly to amethod and process for forming a stent that is at least partially foamedof a novel molybdenum and rhenium metal alloy.

BACKGROUND OF THE INVENTION

Medical treatment of various illnesses or diseases commonly includes theuse of one or more medical devices. Two types of medical devices thatare commonly used to repair various types of body passageways are anexpandable graft or stent, or a surgical graft. These devices have beenimplanted in various areas of the mammalian anatomy. One purpose of astent is to open a blocked or partially blocked body passageway. When astent is used in a blood vessel, the stent is used to open the occludedvessel to achieve improved blood flow which is necessary to provide forthe anatomical function of an organ. The procedure of opening a blockedor partially blocked body passageway commonly includes the use of one ormore stents in combination with other medical devices such as, but notlimited to, an introducer sheath, a guiding catheter, a guide wire, anangioplasty balloon, etc.

Various physical attributes of a stent can contribute directly to thesuccess rate of the device. These physical attributes includeradiopacity, hoop strength, radial force, thickness of the metal,dimensions of the metal and the like. Cobalt and chromium alloys andstainless steel are commonly used to form in stents. These materials arecommonly used since such materials have a known history of safety,effectiveness and biocompatibility. These materials however have limitedphysical performance characteristics as to size, strength, weight,bendability, biostability and radiopacity.

The present invention is generally directed to a method and process formanufacturing and producing a medical device, and more particularlydirected to a method and process for manufacturing and producing a stentthat is at least partially formed of a novel metal alloy.

SUMMARY OF THE INVENTION

The present invention is generally directed to a medical device that isat least partially made of a metal alloy having improved properties ascompared to past medical devices. The metal alloy used to at leastpartially form the medical device improves one or more properties (e.g.,strength, durability, hardness, biostability, bendability, coefficientof friction, radial strength, flexibility, tensile strength, tensileelongation, longitudinal lengthening, stress-strain properties, improvedrecoil properties, radiopacity, heat sensitivity, biocompatibility,etc.) of such medical device. These one or more improved physicalproperties of the metal alloy can be achieved in the medical devicewithout having to increase the bulk, volume and/or weight of the medicaldevice, and in some instances these improved physical properties can beobtained even when the volume, bulk and/or weight of the medical deviceis reduced as compared to medical devices that are at least partiallyformed from traditional stainless steel or cobalt and chromium alloymaterials. The metal alloy that is used to at least partially form themedical device can thus 1) increase the radiopacity of the medicaldevice, 2) increase the radial strength of the medical device, 3)increase the yield strength and/or ultimate tensile strength of themedical device, 4) improve the stress-strain properties of the medicaldevice, 5) improve the crimping and/or expansion properties of themedical device, 6) improve the bendability and/or flexibility of themedical device, 7) improve the strength and/or durability of the medicaldevice, 8) increase the hardness of the medical device, 9) improve thelongitudinal lengthening properties of the medical device, 10) improvethe recoil properties of the medical device, 11) improve the frictioncoefficient of the medical device, 12) improve the heat sensitivityproperties of the medical device, 13) improve the biostability and/orbiocompatibility properties of the medical device, and/or 14) enablesmaller, thinner and/or lighter weight medical devices to be made. Themedical device generally includes one or more materials that impart thedesired properties to the medical device so as to withstand themanufacturing processes that are needed to produce the medical device.These manufacturing processes can include, but are not limited to, lasercutting, etching, crimping, annealing, drawing, pilgering,electroplating, electro-polishing, chemical polishing, cleaning,pickling, ion beam deposition or implantation, sputter coating, vacuumdeposition, etc.

In one non-limiting aspect of the present invention, a medical devicethat can include the metal alloy is a stent for use in a bodypassageway; however, it can be appreciated that other types of medicaldevices could be at least partially formed from the metal alloy. As usedherein, the term “body passageway” is defined to be any passageway orcavity in a living organism (e.g., bile duct, bronchial tubes, nasalcavity, blood vessels, heart, esophagus, trachea, stomach, fallopiantube, uterus, ureter, urethra, the intestines, lymphatic vessels, nasalpassageways, eustachian tube, acoustic meatus, etc.). The techniquesemployed to deliver the medical device to a treatment area include, butare not limited to, angioplasty, vascular anastomoses, interventionalprocedures, and any combinations thereof For vascular applications, theterm “body passageway” primarily refers to blood vessels and chambers inthe heart. The stent can be an expandable stent that is expandable by aballoon and/or other means. The stent can have many shapes and forms.Such shapes can include, but are not limited to, stents disclosed inU.S. Pat. Nos. 6,206,916 and 6,436,133; and PCT Patent Publication No.WO 2008/008529 published Jan. 17, 2008; and all the prior art cited inthese patents. These various designs and configurations of stents insuch patents are incorporated herein by reference.

In another and/or alternative non-limiting aspect of the presentinvention, the medical device is generally designed to include at leastabout 25 weight percent of the metal alloy; however, this is notrequired. In one non-limiting embodiment of the invention, the medicaldevice includes at least about 40 weight percent of the metal alloy. Inanother and/or alternative non-limiting embodiment of the invention, themedical device includes at least about 50 weight percent of the metalalloy. In still another and/or alternative non-limiting embodiment ofthe invention, the medical device includes at least about 60 weightpercent of the metal alloy. In yet another and/or alternativenon-limiting embodiment of the invention, the medical device includes atleast about 70 weight percent of the metal alloy. In still yet anotherand/or alternative non-limiting embodiment of the invention, the medicaldevice includes at least about 85 weight percent of the metal alloy. Ina further and/or alternative non-limiting embodiment of the invention,the medical device includes at least about 90 weight percent of themetal alloy. In still a further and/or alternative non-limitingembodiment of the invention, the medical device includes at least about95 weight percent of the metal alloy. In yet a further and/oralternative non-limiting embodiment of the invention, the medical deviceincludes about 100 weight percent of the metal alloy.

In still another and/or alternative non-limiting aspect of the presentinvention, the metal alloy that is used to form all or part of themedical device 1) is not clad, metal sprayed, plated and/or formed(e.g., cold worked, hot worked, etc.) onto another metal, or 2) does nothave another metal or metal alloy metal sprayed, plated, clad and/orformed onto the metal alloy. It will be appreciated that in someapplications, the metal alloy of the present invention may be clad,metal sprayed, plated and/or formed onto another metal, or another metalor metal alloy may be plated, metal sprayed, clad and/or formed onto themetal alloy when forming all or a portion of a medical device:

In yet another and/or alternative non-limiting aspect of the presentinvention, the metal alloy that is used to form all or a portion of themedical device includes rhenium and molybdenum. The novel alloy caninclude one or more other metals such as, but not limited to, boron,calcium, chromium, cobalt, copper, gold, iron, lead, magnesium,manganese, nickel, niobium, platinum, rare earth metals, silicon,silver, tantalum, tin, titanium, tungsten, yttrium, zinc, zirconium,and/or alloys thereof.

In still yet another and/or alternative non-limiting aspect of thepresent invention, the metal alloy that is used to form all or a portionof the medical device includes tantalum and tungsten. The metal alloycan include one or more other metals such as, but not limited to,calcium, chromium, cobalt, copper, gold, iron, lead, magnesium,molybdenum, nickel, niobium, platinum, rare earth metals, silver,rhenium, titanium, yttrium, zinc, zirconium, and/or alloys thereof. Inone non-limiting embodiment of the invention, the tantalum and tungstenconstitute a majority weight percent of the metal alloy. In anotherand/or alternative non-limiting embodiment of the invention, thetantalum and tungsten content of the metal alloy is at least about 80weight percent. In still another and/or alternative non-limitingembodiment of the invention, the tantalum and tungsten content of themetal alloy is at least about 90 weight percent. In yet another and/oralternative non-limiting embodiment of the invention, the tantalum andtungsten content of the metal alloy is at least about 95 weight percent.In still yet another and/or alternative non-limiting embodiment of theinvention, the tantalum and tungsten content of the metal alloy is atleast about 99 weight percent. In another and/or alternativenon-limiting embodiment of the invention, the tantalum and tungstencontent of the metal alloy is at least about 99.9 weight percent. Instill another and/or alternative non-limiting embodiment of theinvention, the tantalum and tungsten content of the metal alloy is atleast about 99.95 weight percent. In yet a further and/or alternativenon-limiting embodiment of the invention, the content of the tantalumand tungsten content of the metal alloy is at least about 99.99 weightpercent. As can be appreciated, other weight percentages of the tantalumand tungsten content of the metal alloy can be used. In another and/oralternative one non-limiting embodiment of the invention, the metalalloy of tantalum and tungsten includes at least about 0.5 weightpercent tungsten and at least about 10 weight percent tantalum. In stillanother and/or alternative one non-limiting embodiment of the invention,the metal alloy of tantalum and tungsten includes at least about 2weight percent tungsten and at least about 20 weight percent tantalum.In yet another and/or alternative one non-limiting embodiment of theinvention, the metal alloy of tantalum and tungsten includes at leastabout 2.5 weight percent tungsten and at least about 50 weight percenttantalum. In still yet another and/or alternative one non-limitingembodiment of the invention, the metal alloy of tantalum and tungstenincludes about 3-20 weight percent tungsten and about 80-97 weightpercent tantalum. As can be appreciated, other weight percentages oftantalum and tungsten content of the metal alloy can be used.

In still another and/or alternative non-limiting aspect of the presentinvention, the metal alloy that is used to fog in all or a portion ofthe medical device is a metal alloy that includes at least about 90weight percent molybdenum and rhenium. In one non-limiting composition,the content of molybdenum and rhenium in the metal alloy is at leastabout 95 weight percent. In another and/or alternative non-limitingcomposition, the content of molybdenum and rhenium in the metal alloy isat least about 97 weight percent. In still another and/or alternativenon-limiting composition, the content of molybdenum and rhenium in themetal alloy is at least about 98 weight percent. In yet another and/oralternative non-limiting composition, the content of molybdenum andrhenium in the metal alloy is at least about 99 weight percent. In stillyet another and/or alternative non-limiting composition, the content ofmolybdenum and rhenium in the metal alloy is at least about 99.5 weightpercent. In a further one non-limiting composition, the content ofmolybdenum and rhenium in the metal alloy is at least about 99.9 weightpercent. In still a further and/or alternative non-limiting composition,the content of molybdenum and rhenium in the metal alloy is at leastabout 99.95 weight percent. In yet a further and/or alternativenon-limiting composition, the content of molybdenum and rhenium in themetal alloy is at least about 99.99 weight percent. As can beappreciated, other weight percentages of the rhenium and molybdenumcontent of the metal alloy can be used. In one non-limiting composition,the purity level of the metal alloy is such so as to produce a solidsolution of the metal alloy. A solid solution or homogeneous solution isdefined as a metal alloy that includes two or more primary metals andthe combined weight percent of the primary metals is at least about 95weight percent, typically at least about 99 weight percent, moretypically at least about 99.5 weight percent, even more typically atleast about 99.8 weight percent, and still even more typically at leastabout 99.9 weight percent. A primary metal is a metal component of themetal alloy that is not a metal impurity. A solid solution of a metalalloy that includes rhenium and molybdenum as the primary metals is analloy that includes at least about 95-99 weight percent rhenium andmolybdenum. It is believed that a purity level of less than 95 weightpercent molybdenum and rhenium adversely affects one or more physicalproperties of the metal alloy that are useful or desired in formingand/or using a medical device. In one embodiment of the invention, therhenium content of the metal alloy in accordance with the presentinvention is at least about 40 weight percent. In one non-limitingcomposition, the rhenium content of the metal alloy is at least about 41weight percent. In another and/or alterative non-limiting composition,the rhenium content of the metal alloy is at least about 45 weightpercent. In still another and/or alternative non-limiting composition,the rhenium content of the metal alloy is about 45-50 weight percent. Inyet another and/or alternative non-limiting composition, the rheniumcontent of the metal alloy is about 47-48 weight percent. In still yetanother and/or alternative non-limiting composition, the rhenium contentof the metal alloy is about 47.6-49.5 weight percent. In still anotherand/or alternative non-limiting composition, the rhenium content of themetal alloy is about 47.15-47.5 weight percent. As can be appreciated,other weight percentages of the rhenium content of the metal alloy canbe used. In another and/or alternative embodiment of the invention, themolybdenum content of the metal alloy in accordance with the presentinvention is at least about 40 weight percent. In one non-limitingcomposition, the molybdenum content of the metal alloy is at least about45 weight percent. In another and/or alternative non-limitingcomposition, the molybdenum content of the metal alloy is at least about50 weight percent. In still another and/or alternative non-limitingcomposition, the molybdenum content of the metal alloy is about 50-60percent. In yet another and/or alternative non-limiting composition, themolybdenum content of the metal alloy is about 51-59 weight percent. Instill yet another and/or alternative non-limiting composition, themolybdenum content of the metal alloy is about 50-56 weight percent. Ascan be appreciated, other weight percentages of the molybdenum contentof the metal alloy can be used.

In still yet another and/or alternative non-limiting aspect of thepresent invention, the metal alloy that is used to form all or a portionof the medical device is a metal alloy that includes at least about 90weight percent molybdenum and rhenium, and at least one additional metalwhich includes titanium, yttrium, and/or zirconium. The addition ofcontrolled amounts of titanium, yttrium, and/or zirconium to themolybdenum and rhenium alloy has been found to form a metal alloy thathas improved physical properties over a metal alloy that principallyincludes molybdenum and rhenium. For instance, the addition ofcontrolled amounts of titanium, yttrium, and/or zirconium to themolybdenum and rhenium alloy can result in 1) an increase in yieldstrength of the alloy as compared to a metal alloy that principallyincludes molybdenum and rhenium, 2) an increase in tensile elongation ofthe alloy as compared to a metal alloy that principally includesmolybdenum and rhenium, 3) an increase in ductility of the alloy ascompared to a metal alloy that principally includes molybdenum andrhenium, 4) a reduction in grain size of the alloy as compared to ametal alloy that principally includes molybdenum and rhenium, 5) areduction in the amount of free carbon, oxygen and/or nitrogen in thealloy as compared to a metal alloy that principally includes molybdenumand rhenium, and/or 6) a reduction in the tendency of the alloy to formmicro-cracks during the forming of the alloy into a medical device ascompared to the forming of a medical device from a metal alloy thatprincipally includes molybdenum and rhenium. In one non-limitingcomposition, the content of molybdenum and rhenium and the at least oneadditional metal in the metal alloy is at least about 90 weight percent.In another and/or alternative non-limiting composition, the content ofmolybdenum and rhenium and the at least one additional metal in themetal alloy is at least about 95 weight percent. In still another and/oralternative non-limiting composition, the content of molybdenum andrhenium and the at least one additional metal in the metal alloy is atleast about 98 weight percent. In yet another and/or alternativenon-limiting composition, the content of molybdenum and rhenium and theat least one additional metal in the metal alloy is at least about 99weight percent. In still yet another and/or alternative non-limitingcomposition, the content of molybdenum and rhenium and the at least oneadditional metal in the metal alloy is at least about 99.5 weightpercent. In a further one non-limiting composition, the content ofmolybdenum and rhenium and the at least one additional metal in themetal alloy is at least about 99.9 weight percent. In still a furtherand/or alternative non-limiting composition, the content of molybdenumand rhenium and the at least one additional metal in the metal alloy isat least about 99.95 weight percent. In yet a further and/or alternativenon-limiting composition, the content of molybdenum and rhenium and theat least one additional metal in the metal alloy is at least about 99.99weight percent. As can be appreciated, other weight percentages of thecontent of molybdenum and rhenium and the at least one additional metalin the metal alloy can be used. In one non-limiting composition, thepurity level of the metal alloy is such so as to produce a solidsolution of a rhenium and molybdenum and the at least one additionalmetal. A solid solution of a metal alloy that includes rhenium andmolybdenum and the at least one additional metal of titanium, yttriumand/or zirconium as the primary metals is an alloy that includes atleast about 95-99 weight percent rhenium and molybdenum and the at leastone additional metal. It is believed that a purity level of less than 95weight percent molybdenum and rhenium and the at least one additionalmetal adversely affects one or more physical properties of the metalalloy that are useful or desired in forming and/or using a medicaldevice. In one embodiment of the invention, the rhenium content of themetal alloy in accordance with the present invention is at least about40 weight percent. In one non-limiting composition, the rhenium contentof the metal alloy is at least about 45 weight percent. In still anotherand/or alternative non-limiting composition, the rhenium content of themetal alloy is about 45-50 weight percent. In yet another and/oralternative non-limiting composition, the rhenium content of the metalalloy is about 47-48 weight percent. As can be appreciated, other weightpercentages of the rhenium content of the metal alloy can be used. Inanother and/or alternative embodiment of the invention, the molybdenumcontent of the metal alloy is at least about 40 weight percent. In onenon-limiting composition, the molybdenum content of the metal alloy isat least about 45 weight percent. In another and/or alternativenon-limiting composition, the molybdenum content of the metal alloy isat least about 50 weight percent. In still another and/or alternativenon-limiting composition, the molybdenum content of the metal alloy isabout 50-60 percent. In yet another and/or alternative non-limitingcomposition, the molybdenum content of the metal alloy is about 50-56weight percent. As can be appreciated, other weight percentages of themolybdenum content of the metal alloy can be used. The combined contentof titanium, yttrium and zirconium in the metal alloy is less than about5 weight percent, typically no more than about 1 weight percent, andmore typically no more than about 0.5 weight percent. A higher weightpercent content of titanium, yttrium and/or zirconium in the metal alloycan begin to adversely affect the brittleness of the metal alloy. Whentitanium is included in the metal alloy, the titanium content istypically less than about 1 weight percent, more typically less thanabout 0.6 weight percent, even more typically about 0.05-0.5 weightpercent, still even more typically about 0.1-0.5 weight percent. As canbe appreciated, other weight percentages of the titanium content of themetal alloy can be used. When zirconium is included in the metal alloy,the zirconium content is typically less than about 0.5 weight percent,more typically less than about 0.3 weight percent, even more typicallyabout 0.01-0.25 weight percent, still even more typically about0.05-0.25 weight percent. As can be appreciated, other weightpercentages of the zirconium content of the metal alloy can be used.When titanium and zirconium are included in the metal alloy, the weightratio of titanium to zirconium is about 1-10:1, typically about 1.5-5:1,and more typically about 1.75-2.5:1. When yttrium is included in themetal alloy, the yttrium content is typically less than about 0.3 weightpercent, more typically less than about 0.2 weight percent, and evenmore typically about 0.01-0.1 weight percent. As can be appreciated,other weight percentages of the yttrium content of the metal alloy canbe used. The inclusion of titanium, yttrium and/or zirconium in themetal alloy is believed to result in a reduction of oxygen trapped inthe solid solution of the metal alloy. The reduction of trapped oxygenenables the formation of a smaller grain size in the metal alloy and/oran increase in the ductility of the metal alloy. The reduction oftrapped oxygen in the metal alloy can also increase the yield strengthof the metal alloy as compared to alloys of only molybdenum and rhenium(i.e., 2-10% increase). The inclusion of titanium, yttrium and/orzirconium in the metal alloy is also believed to cause a reduction inthe trapped free carbon in the metal alloy. The inclusion of titanium,yttrium and/or zirconium in the metal alloy is believed to form carbideswith the free carbon in the metal alloy. This carbide formation is alsobelieved to improve the ductility of the metal alloy and to also reducethe incidence of cracking during the forming of the metal alloy into amedical device (e.g., stent, etc.). As such, the metal alloy exhibitsincreased tensile elongation as compared to alloys of only molybdenumand rhenium (i.e., 1-8% increase). The inclusion of titanium, yttriumand/or zirconium in the metal alloy is also believed to cause areduction in the trapped free nitrogen in the metal alloy. The inclusionof titanium, yttrium and/or zirconium in the metal alloy is believed toform carbo-nitrides with the free carbon and free nitrogen in the metalalloy. This carbo-nitride formation is also believed to improve theductility of the metal alloy and to also reduce the incidence ofcracking during the forming of the metal alloy into a medical device(e.g., stent, etc.). As such, the metal alloy exhibits increased tensileelongation as compared to alloys of only molybdenum and rhenium (i.e.,1-8% increase). The reduction in the amount of free carbon, oxygenand/or nitrogen in the metal alloy is also believed to increase thedensity of the metal alloy (i.e., 1-5% increase). The formation ofcarbides, carbo-nitrides, and/or oxides in the metal alloy results inthe formation of dispersed second phase particles in the metal alloy,thereby facilitating in the formation of small grain sizes in the metalalloy.

In still another and/or alternative non-limiting aspect of the presentinvention, the metal alloy includes less than about 5 weight percentother metals and/or impurities. A high purity level of the metal alloyresults in the formation of a more homogeneous alloy, which in turnresults in a more uniform density throughout the metal alloy, and alsoresults in the desired yield and ultimate tensile strengths of the metalalloy. The density of the metal alloy is generally at least about 12gm/cc., and typically at least about 13-13.5 gm/cc. This substantiallyuniform high density of the metal alloy significantly improves theradiopacity of the metal alloy. In one non-limiting composition, themetal alloy includes less than about 1 weight percent other metalsand/or impurities. In another and/or alternative non-limitingcomposition, the metal alloy includes less than about 0.5 weight percentother metals and/or impurities. In still another and/or alternativenon-limiting composition, the metal alloy includes less than about 0.4weight percent other metals and/or impurities. In yet another and/oralternative non-limiting composition, the metal alloy includes less thanabout 0.2 weight percent other metals and/or impurities. In still yetanother and/or alternative non-limiting composition, the metal alloyincludes less than about 0.1 weight percent other metals and/orimpurities. In a further and/or alternative non-limiting composition,the metal alloy includes less than about 0.05 weight percent othermetals and/or impurities. In still a further and/or alternativenon-limiting composition, the metal alloy includes less than about 0.02weight percent other metals and/or impurities. In yet a further and/oralternative non-limiting composition, the metal alloy includes less thanabout 0.01 weight percent other metals and/or impurities. As can beappreciated, other weight percentages of the amount of other metalsand/or impurities in the metal alloy can exist.

In yet another and/or alternative non-limiting aspect of the presentinvention, the metal alloy includes a certain amount of carbon andoxygen. These two elements have been found to affect the formingproperties and brittleness of the metal alloy. The controlled atomicratio of carbon and oxygen in the metal alloy also can be used tominimize the tendency of the metal alloy to foam micro-cracks during theforming of the novel alloy into a medical device, and/or during the useand/or expansion of the medical device in a body passageway. The controlof the atomic ratio of carbon to oxygen in the metal alloy allows forthe redistribution of oxygen in the metal alloy so as to minimize thetendency of micro-cracking in the metal alloy during the forming of themetal alloy into a medical device, and/or during the use and/orexpansion of the medical device in a body passageway. The atomic ratioof carbon to oxygen in the alloy is believed to be important to minimizethe tendency of micro-cracking in the metal alloy, improve the degree ofelongation of the metal alloy, both of which can affect one or morephysical properties of the metal alloy that are useful or desired informing and/or using the medical device. It was previously believed byapplicants that a carbon to oxygen atomic ratio of less than about 2:1would adversely affect the properties of a medical device such as, butnot limited to a stent. Upon further investigation, it has been foundthat a stent when exposed to body temperatures can be formed of themetal alloy with a carbon to oxygen atomic ratio that is less than about2:1; however, it is still believed that the properties of the stent arebetter when the carbon to oxygen atomic ratio is greater than about 2:1.It is believed that for certain applications of the metal alloy whenoperating in temperatures of about 40-120° F. and that the oxygencontent is below a certain amount, the carbon to oxygen atomic ratio canbe as low as about 0.2:1. In one non-limiting formulation, the carbon tooxygen atomic ratio in the metal alloy is generally at least about 0.4:1(i.e., weight ratio of about 0.3:1). In another non-limitingformulation, the carbon to oxygen atomic ratio in the metal alloy isgenerally at least about 0.5:1 (i.e., weight ratio of about 0.375:1). Instill another non-limiting formulation, the carbon to oxygen atomicratio in the metal alloy is generally at least about 1:1 (i.e., weightratio of about 0.75:1). In yet another non-limiting formulation, thecarbon to oxygen atomic ratio in the metal alloy is generally at leastabout 2:1 (i.e., weight ratio of about 1.5:1). In still yet anothernon-limiting formulation, the carbon to oxygen atomic ratio in the metalalloy is generally at least about 2.5:1 (i.e., weight ratio of about1.88:1). In still another non-limiting formulation, the carbon to oxygenatomic ratio in the metal alloy is generally at least about 3:1 (i.e.,weight ratio of about 2.25:1). In yet another non-limiting formulation,the carbon to oxygen atomic ratio in the metal alloy is generally atleast about 4:1 (i.e., weight ratio of about 3:1). In still yet anothernon-limiting formulation, the carbon to oxygen atomic ratio in the metalalloy is generally at least about 5:1 (i.e., weight ratio of about3.75:1). In still another non-limiting formulation, the carbon to oxygenatomic ratio in the metal alloy is generally about 2.5-50:1 (i.e.,weight ratio of about 1.88-37.54:1). In a further non-limitingformulation, the carbon to oxygen atomic ratio in the metal alloy isgenerally about 2.5-20:1 (i.e., weight ratio of about 1.88-15:1). In afurther non-limiting formulation, the carbon to oxygen atomic ratio inthe metal alloy is generally about 2.5-13.3:1 (i.e., weight ratio ofabout 1.88-10:1). In still a further non-limiting formulation, thecarbon to oxygen atomic ratio in the metal alloy is generally about2.5-10:1 (i.e., weight ratio of about 1.88-7.5:1). In yet a furthernon-limiting formulation, the carbon to oxygen atomic ratio in the metalalloy is generally about 2.5-5:1 (i.e., weight ratio of about1.88-3.75:1). As can be appreciated, other atomic ratios of the carbonto oxygen in the metal alloy can be used. The carbon to oxygen ratio canbe adjusted by intentionally adding carbon to the metal alloy until thedesired carbon to oxygen ratio is obtained. Typically the carbon contentof the metal alloy is less than about 0.2 weight percent. Carboncontents that are too large can adversely affect the physical propertiesof the metal alloy. In one non-limiting formulation, the carbon contentof the metal alloy is less than about 0.1 weight percent of the metalalloy. In another non-limiting formulation, the carbon content of themetal alloy is less than about 0.05 weight percent of the metal alloy.In still another non-limiting formulation, the carbon content of themetal alloy is less than about 0.04 weight percent of the metal alloy.When carbon is not intentionally added to the metal alloy, the metalalloy can include up to about 150 ppm carbon, typically up to about 100ppm carbon, and more typically less than about 50 ppm carbon. The oxygencontent of the metal alloy can vary depending on the processingparameters used to form the metal alloy. Generally, the oxygen contentis to be maintained at very low levels. In one non-limiting formulation,the oxygen content is less than about 0.1 weight percent of the metalalloy. In another non-limiting formulation, the oxygen content is lessthan about 0.05 weight percent of the metal alloy. In still anothernon-limiting formulation, the oxygen content is less than about 0.04weight percent of the metal alloy. In yet another non-limitingformulation, the oxygen content is less than about 0.03 weight percentof the metal alloy. In still yet another non-limiting formulation, themetal alloy includes up to about 100 ppm oxygen. In a furthernon-limiting formulation, the metal alloy includes up to about 75 ppmoxygen. In still a further non-limiting formulation, the metal alloyincludes up to about 50 ppm oxygen. In yet a further non-limitingformulation, the metal alloy includes up to about 30 ppm oxygen. Instill yet a further non-limiting formulation, the metal alloy includesless than about 20 ppm oxygen. In yet a further non-limitingformulation, the metal alloy includes less than about 10 ppm oxygen. Ascan be appreciated, other amounts of carbon and/or oxygen in the metalalloy can exist. It is believed that the metal alloy will have a verylow tendency to form micro-cracks during the formation of the medicaldevice (e.g., stent, etc.) and after the medical device has beeninserted into a patient by closely controlling the carbon to oxygenration when the oxygen content exceed a certain amount in the metalalloy. In one non-limiting arrangement, the carbon to oxygen atomicratio in the metal alloy is at least about 2.5:1 when the oxygen contentis greater than about 100 ppm in the metal alloy.

In still yet another and/or alternative non-limiting aspect of thepresent invention, the metal alloy includes a controlled amount ofnitrogen. Large amounts of nitrogen in the metal alloy can adverselyaffect the ductility of the metal alloy. This can in turn adverselyaffect the elongation properties of the metal alloy. A too high ofnitrogen content in the metal alloy can begin to cause the ductility ofthe metal alloy to unacceptably decrease, thus adversely affect one ormore physical properties of the metal alloy that are useful or desiredin forming and/or using the medical device. In one non-limitingformulation, the metal alloy includes less than about 0.001 weightpercent nitrogen. In another non-limiting formulation, the metal alloyincludes less than about 0.0008 weight percent nitrogen. In stillanother non-limiting formulation, the metal alloy includes less thanabout 0.0004 weight percent nitrogen. In yet another non-limitingformulation, the metal alloy includes less than about 30 ppm nitrogen.In still yet another non-limiting formulation, the metal alloy includesless than about 25 ppm nitrogen. In still another non-limitingformulation, the metal alloy includes less than about 10 ppm nitrogen.In yet another non-limiting formulation, the metal alloy includes lessthan about 5 ppm nitrogen. As can be appreciated, other amounts ofnitrogen in the metal alloy can exist. The relationship of carbon,oxygen and nitrogen in the metal alloy is also believed to be important.It is believed that the nitrogen content should be less than the contentof carbon or oxygen in the metal alloy. In one non-limiting formulation,the atomic ratio of carbon to nitrogen is at least about 2:1 (i.e.,weight ratio of about 1.71:1). In another non-limiting formulation, theatomic ratio of carbon to nitrogen is at least about 3:1 (i.e., weightratio of about 2.57:1). In still another non-limiting formulation, theatomic ratio of carbon to nitrogen is about 4-100:1 (i.e., weight ratioof about 3.43-85.7:1). In yet another non-limiting formulation, theatomic ratio of carbon to nitrogen is about 4-75:1 (i.e., weight ratioof about 3.43-64.3:1). In still another non-limiting formulation, theatomic ratio of carbon to nitrogen is about 4-50:1 (i.e., weight ratioof about 3.43-42.85:1). In yet another non-limiting formulation, theatomic ratio of carbon to nitrogen is about 4-35:1 (i.e., weight ratioof about 3.43-30:1). In still yet another non-limiting formulation, theatomic ratio of carbon to nitrogen is about 4-25:1 (i.e., weight ratioof about 3.43-21.43:1). In a further non-limiting formulation, theatomic ratio of oxygen to nitrogen is at least about 1.2:1 (i.e., weightratio of about 1.37:1). In another non-limiting formulation, the atomicratio of oxygen to nitrogen is at least about 2:1 (i.e., weight ratio ofabout 2.28:1). In still another non-limiting formulation, the atomicratio of oxygen to nitrogen is about 3-100:1 (i.e., weight ratio ofabout 3.42-114.2:1). In yet another non-limiting formulation, the atomicratio of oxygen to nitrogen is at least about 3-75:1 (i.e., weight ratioof about 3.42-85.65:1). In still yet another non-limiting formulation,the atomic ratio of oxygen to nitrogen is at least about 3-55:1 (i.e.,weight ratio of about 3.42-62.81:1). In yet another non-limitingformulation, the atomic ratio of oxygen to nitrogen is at least about3-50:1 (i.e., weight ratio of about 3.42-57.1:1).

In a further and/or alternative non-limiting aspect of the presentinvention, the metal alloy has several physical properties thatpositively affect the medical device when at least partially formed ofthe metal alloy. In one non-limiting embodiment of the invention, theaverage Vickers hardness of the metal alloy tube used to form themedical device is generally at least about 234 DHP (i.e., Rockwell Ahardness of at least about 60 at 77° F., Rockwell C hardness of at leastabout 19 at 77° F). In one non-limiting aspect of this embodiment, theaverage hardness of the metal alloy used to form the medical device isgenerally at least about 248 DHP (i.e., Rockwell A hardness of at leastabout 62 at 77° F., Rockwell C hardness of at least about 22 at 77° F.).In another and/or additional non-limiting aspect of this embodiment, theaverage hardness of the metal alloy used to form the medical device isgenerally about 248-513 DHP (i.e., Rockwell A hardness of about 62-76 at77° F., Rockwell C hardness of about 22-50 at 77° F.). In still anotherand/or additional non-limiting aspect of this embodiment, the averagehardness of the metal alloy used to form the medical device is generallyabout 272-458 DHP (i.e., Rockwell A hardness of about 64-74 at 77° F.,Rockwell C hardness of about 26-46 at 77° F.). When titanium, yttriumand/or zirconium are included in an alloy of molybdenum and rhenium, theaverage hardness of the metal alloy is generally increased. Tungsten andtantalum alloys also generally have an average hardness of the metalalloy that is greater that is slightly greater than pure alloys ofmolybdenum and rhenium. In tungsten and tantalum alloys, and molybdenumand rhenium alloys that include titanium, yttrium and/or zirconium, theaverage hardness is generally at least about 60 (HRC) at 77° F.,typically at least about 70 (HRC) at 77° F., and more typically about80-100 (HRC) at 77° F. In another and/or alternative non-limitingembodiment of the invention, the average ultimate tensile strength ofthe metal alloy used to form the medical device is generally at leastabout 60 UTS (ksi). In non-limiting aspect of this embodiment, theaverage ultimate tensile strength of the metal alloy used to form themedical device is generally at least about 70 UTS (ksi), typically about80-320 UTS (ksi), and more typically about 100-310 UTS (ksi). Theaverage ultimate tensile strength of the metal alloy will very somewhatwhen the metal alloy is in the form of a tube or a solid wire. When themetal alloy is in the form of a tube, the average ultimate tensilestrength of the metal alloy tube is generally about 80-150 UTS (ksi),typically at least about 110 UTS (ksi), and more typically 110-140 UTS(ksi). When the metal alloy is in the form of a solid wire, the averageultimate tensile strength of the metal alloy wire is generally about120-310 UTS (ksi). In still another and/or alternative non-limitingembodiment of the invention, the average yield strength of the metalalloy used to form the medical device is at least about 70 ksi. In onenon-limiting aspect of this embodiment, the average yield strength ofthe metal alloy used to form the medical device is at least about 80ksi, and typically about 100-140 (ksi). In yet another and/oralternative non-limiting embodiment of the invention, the average grainsize of the metal alloy used to form the medical device is no greaterthan about 4 ASTM (e.g., ASTM 112-96). The grain size can be as small asabout 14-15 ASTM can be achieved; however, the grain size is typicallylarger than 15 ASTM. The small grain size of the metal alloy enables themedical device to have the desired elongation and ductility propertiesthat are useful in enabling the medical device to be formed, crimpedand/or expanded. In one non-limiting aspect of this embodiment, theaverage grain size of the metal alloy used to form the medical device isabout 5.2-10 ASTM, typically about 5.5-9 ASTM, more typically about 6-9ASTM, still more typically about 6-9 ASTM, even more typically about6.6-9 ASTM, and still even more typically about 7-8.5 ASTM. In still yetanother and/or alternative non-limiting embodiment of the invention, theaverage tensile elongation of the metal alloy used to form the medicaldevice is at least about 25%. An average tensile elongation of at least25% for the metal alloy is important to enable the medical device to beproperly expanded when positioned in the treatment area of a bodypassageway. A medical device that does not have an average tensileelongation of at least about 25% can fin m micro-cracks and/or breakduring the forming, crimping and/or expansion of the medical device. Inone non-limiting aspect of this embodiment, the average tensileelongation of the metal alloy used to form the medical device is about25-35%. The unique combination of the rhenium and molybdenum or tungstenand tantalum in the metal alloy in combination with achieving thedesired purity and composition of the alloy and the desired grain sizeof the metal alloy results in 1) a medical device having the desiredhigh ductility at about room temperature, 2) a medical device having thedesired amount of tensile elongation, 3) a homogeneous or solid solutionof a metal alloy having high radiopacity, 4) a reduction or preventionof microcrack formation and/or breaking of the metal alloy tube when themetal alloy tube is sized and/or cut to form the medical device, 5) areduction or prevention of microcrack formation and/or breaking of themedical device when the medical device is crimped onto a balloon and/orother type of medical device for insertion into a body passageway, 6) areduction or prevention of microcrack formation and/or breaking of themedical device when the medical device is bent and/or expanded in a bodypassageway, 7) a medical device having the desired ultimate tensilestrength and yield strength, 8) a medical device that can have very thinwall thicknesses and still have the desired radial forces needed toretain the body passageway on an open state when the medical device hasbeen expanded, and/or 9) a medical device that exhibits less recoil whenthe medical device is crimped onto a delivery system and/or expanded ina body passageway.

Several non-limiting examples of the metal alloy that can be made inaccordance with the present invention are set forth below:

Metal/Wt. % Ex. 1 Ex. 2 Ex.3 C <150 ppm <50 ppm <50 ppm Mo 51-54%52.5-55.5% 50.5-52.4% O  <50 ppm <10 ppm <10 ppm N  <20 ppm <10 ppm <10ppm Re 46-49% 44.5-47.5% 47.6-49.5% Metal/Wt. % Ex. 4 Ex. 5 Ex. 6 Ex. 7C ≦50 ppm ≦50 ppm ≦50 ppm ≦50 ppm Mo 51-54% 52.5-55.5% 52-56% 52.5-55%  O ≦20 ppm ≦20 ppm ≦10 ppm ≦10 ppm N ≦20 ppm ≦20 ppm ≦10 ppm ≦10 ppm Re46-49% 44.5-47.5% 44-48%   45-47.5% Ti ≦0.4% ≦0.4% 0.2-0.4% 0.3-0.4% Y≦0.1% ≦0.1%   0-0.08% 0.005-0.05%  Zr ≦0.2% ≦0.2%   0-0.2%  0.1-0.25%Metal/Wt. % Ex. 8 Ex. 9 Ex. 10 Ex. 11 C ≦40 ppm ≦40 ppm ≦40 ppm ≦40 ppmMo 50.5-53%   51.5-54%   52-55% 52.5-55%   O ≦15 ppm ≦15 ppm ≦15 ppm ≦10ppm N ≦10 ppm ≦10 ppm ≦10 ppm ≦10 ppm Re   47-49.5%   46-48.5% 45-48%  45-47.5% Ti  0.1-0.35% 0% 0% 0.1-0.3% Y 0% 0.002-0.08%  0% 0% Zr 0% 0%00.1-0.2% 0.05-0.15% Metal/Wt. % Ex. 12 Ex. 13 Ex. 14 Ex. 15 C ≦40 ppm≦40 ppm <150 ppm <150 ppm Mo 52-55% 52.5-55.5% 50-60% 50-60% O ≦10 ppm≦10 ppm ≦100 ppm ≦100 ppm N ≦10 ppm ≦10 ppm  ≦40 ppm  ≦40 ppm Re 45-49%44.5-47.5% 40-50% 40-50% Ti 0.05-0.4%  0% 0% ≦1% Y 0.005-0.07% 0.004-0.06%  0% ≦0% Zr 0% 0.1-0.2% 0% ≦2% Metal/Wt. % Ex. 16. Ex. 17 Ex.18 Ex. 19 C ≦150 ppm ≦150 ppm ≦150 ppm ≦150 ppm Mo 50-55% 52-55.5%51-58% 50-56% O ≦100 ppm ≦100 ppm ≦100 ppm ≦100 ppm N  ≦40 ppm  ≦20 ppm ≦20 ppm  ≦20 ppm Re 45-50% 44.5-48%   42-49% 44-50% Ti 0% 0% 0% 0% Y 0%0% 0% 0% Zr 0% 0% 0% 0% Metal/Wt. % Ex. 20 Ex. 21 Ex. 22 C <150 ppm <50ppm <50ppm Mo 51-54% 52.5-55.5% 50.5-52.4% O  <50 ppm <10 ppm <10 ppm N <20 ppm <10 ppm <10 ppm Re 46-49% 44.5-47.5% 47.6-49.5% Ti 0% 0% 0% Y0% 0% 0% Zr 0% 0% 0% Metal/Wt. % Ex. 23 Ex. 24 Ex. 25 C ≦150 ppm ≦150ppm ≦150 ppm Mo 50-60% 50-60% 50-55% O ≦100 ppm ≦100 ppm ≦100 ppm N  ≦40ppm  ≦40 ppm  ≦40 ppm Re 40-50% 40-50% 45-50% Ti  ≦0.5%  ≦0.5%  ≦0.5% Y ≦0.1%  ≦0.1%  ≦0.1% Zr ≦0.25% ≦0.25% ≦0.25% Metal/Wt. % Ex. 26 Ex. 27Ex. 28 C ≦150 ppm ≦150 ppm ≦150 ppm Mo   52-55.5% 51-58% 50-56% O ≦100ppm ≦100 ppm ≦100 ppm N  ≦20 ppm  ≦20 ppm  ≦20 ppm Re 44.5-48%   42-49%44-50% Ti  ≦0.5%  ≦0.5%  ≦0.5% Y  ≦0.1%  ≦0.1%  ≦0.1% Zr ≦0.25% ≦0.25%≦0.25% Metal/Wt. % Ex. 29 Ex. 30 Ex. 31 Ex. 32 C ≦50 ppm ≦50 ppm ≦50 ppm≦50 ppm Mo 51-54% 52.5-55.5% 52-56% 52.5-55%   O ≦20 ppm ≦20 ppm ≦10 ppm≦10 ppm N ≦20 ppm ≦20 ppm ≦10 ppm ≦10 ppm Re 46-49% 44.5-47.5% 44-48%  45-47.5% Ti ≦0.4% ≦0.4% 0.2-0.4% 0.3-0.4% Y ≦0.1% ≦0.1%    0-0.08%0.005-0.05%  Zr ≦0.2% ≦0.2%   0-0.2%  0.1-0.25% Metal/Wt. % Ex. 33 Ex.34 Ex. 35 Ex. 36 C ≦40 ppm ≦40 ppm ≦40 ppm ≦40 ppm Mo 50.5-53%  51.5-54%   52-55% 52.5-55%   O ≦15 ppm ≦15 ppm ≦15 ppm ≦10 ppm N ≦10 ppm≦10 ppm ≦10 ppm ≦10 ppm Re   47-49.5%   46-48.5% 45-48%   45-47.5% Ti 0.1-0.35% 0% 0% 0.1-0.3% Y 0% 0.002-0.08%  0% 0% Zr 0% 0% 0.01-0.2%  0.05-0.15% Metal/Wt. % Ex. 37 Ex. 38 C ≦40 ppm ≦40 ppm Mo 52-55%52.5-55.5% O ≦10 ppm ≦10 ppm N ≦10 ppm ≦10 ppm Re 45-49% 44.5-47.5% Ti0.05-0.4%  0% Y 0.005-0.07%   0.004-0.06%  Zr 0% 0.1-0.2% Metal/Wt. %Ex. 39 C ≦150 ppm Mo 50-60% O ≦100 ppm N  ≦40 ppm Nb     ≦5% Rare EarthMetal     ≦4% Re 40-50% Ta     ≦3% Ti     ≦1% W     ≦3% Y   ≦0.1% Zn  ≦0.1% Zr      ≦2% Metal/Wt. % Ex. 40 C   ≦0.01% Co  ≦0.002% Fe  ≦0.02% H  ≦0.002% Mo 52-53% N ≦0.0008% Ni   ≦0.01% O   ≦0.06% Re47-48% S  ≦0.008% Sn  ≦0.002% Ti  ≦0.002% W   ≦0.02% Metal/Wt. % Ex. 41Ex. 42 Ex. 43 Ex.44 C 0-50 ppm 0-50 ppm 0-50 ppm 0-50 ppm Ca 0-1%  0-0.5% 0% 0% Mg 0% 0-3% 0% 0% Mo 0% 0-2% 0% 0% O 0-50 ppm 0-50 ppm0-50 ppm 0-50 ppm N 0-50 ppm 0-50 ppm 0-50 ppm 0-50 ppm Rare Earth Metal0-1%   0-0.5% 0% 0% Re 0-6% 0-5% 0-4% 0% Ta 85-96% 10-90% 85-95%90.5-98% W  4-15% 10-90%  5-15%   2-9.5% Y 0% 0-1% 0% 0% Zn 0% 0-1% 0%0% Zr 0% 0-1% 0% 0% Metal/Wt. % Ex. 45 Ex.46 C 0-50 ppm 0-50 ppm Ca 0%0% Mg 0% 0% Mo 0% 0% O 0-50 ppm 0-50 ppm N 0-50 ppm 0-50 ppm Rare EarthMetal 0% 0% Re 0-4% 0% Ta 95-98% 90-97.5% W 2% to less than 5% 2.5-10% Y 0% 0% Zn 0% 0% Zr 0% 0%

In examples 1-3, 14, 16-19, and 20-22 above, the metal alloy isprincipally formed of rhenium and molybdenum and the content of othermetals and/or impurities is less than about 0.1 weight percent of themetal alloy, the atomic ratio of carbon to oxygen is about 2.5-10:1(i.e., weight ratio of about 1.88-7.5:1), the average grain size of themetal alloy is about 6-10 ASTM, the tensile elongation of the metalalloy is about 25-35%, the average density of the metal alloy is atleast about 13.4 gm/cc, the average yield strength of the metal alloy isabout 98-122 (ksi), the average ultimate tensile strength of the metalalloy is about 150-310 UTS (ksi), and an average Vickers hardness of372-653 (i.e., Rockwell A Hardness of about 70-80 at 77° F., an averageRockwell C Hardness of about 39-58 at 77° F.). In examples 4-7, 8-11,12, 13, 15, and 32-38 above, the metal alloy is principally formed ofrhenium and molybdenum and at least one metal of titanium, yttriumand/or zirconium, and the content of other metals and/or impurities isless than about 0.1 weight percent of the metal alloy, the ratio ofcarbon to oxygen is about 2.5-10:1, the average grain size of the metalalloy is about 6-10 ASTM, the tensile elongation of the metal alloy isabout 25-35%, the average density of the metal alloy is at least about13.6 gm/cc, the average yield strength of the metal alloy is at leastabout 110 (ksi), the average ultimate tensile strength of the metalalloy is about 150-310 UTS (ksi), and an average Vickers hardness of372-653 (i.e., an average Rockwell A Hardness of about 70-80 at 77° F.,an average Rockwell C Hardness of about 39-58 at 77° F.). The remainingalloys identified in the above examples may or may not include titanium,yttrium and/or zirconium. The properties of these alloys will be similarto the alloys discussed in the above examples. In example 32, the weightratio of titanium to zirconium is about 1.5-3:1. In example 36, theweight ratio of titanium to zirconium is about 1.75-2.5:1. In examples29-32, the weight ratio of titanium to zirconium is about 1-10:1. Inexample 40, the ratio of carbon to oxygen is at least about 0.4:1 (i.e.,weight ratio of carbon to oxygen of at least about 0.3:1), the nitrogencontent is less than the carbon content and the oxygen content, theatomic ratio of carbon to nitrogen is at least about 4:1 (i.e., weightratio of about 3.43:1), the atomic ratio of oxygen to nitrogen is atleast about 3:1 (i.e., weight ratio of about 3.42:1), the average grainsize of metal alloy is about 6-10 ASTM, the tensile elongation of themetal alloy is about 25-35%, the average density of the metal alloy isat least about 13.4 gm/cc, the average yield strength of the metal alloyis about 98-122 (ksi), the average ultimate tensile strength of themetal alloy is about 100-150 UTS (ksi), and the average hardness of themetal alloy is about 80-100 (HRC) at 77° F.

In examples 41-46, the metal alloy is principally formed of tungsten andtantalum and the content of other metals and/or impurities is less thanabout 0.1 weight percent, and typically less than 0.04 weight percent ofthe metal alloy.

In another and/or alternative non-limiting aspect of the presentinvention, the use of the metal alloy in the medical device can increasethe strength of the medical device as compared with stainless steel orchromium-cobalt alloys, thus less quantity of metal alloy can be used inthe medical device to achieve similar strengths as compared to medicaldevices formed of different metals. As such, the resulting medicaldevice can be made smaller and less bulky by use of the metal alloywithout sacrificing the strength and durability of the medical device.Such a medical device can have a smaller profile, thus can be insertedin smaller areas, openings and/or passageways. The metal alloy also canincrease the radial strength of the medical device. For instance, thethickness of the walls of the medical device and/or the wires used toform the medical device can be made thinner and achieve a similar orimproved radial strength as compared with thicker walled medical devicesformed of stainless steel or cobalt and chromium alloy. The metal alloyalso can improve stress-strain properties, bendability and flexibilityof the medical device, thus increase the life of the medical device. Forinstance, the medical device can be used in regions that subject themedical device to bending. Due to the improved physical properties ofthe medical device from the metal alloy, the medical device has improvedresistance to fracturing in such frequent bending environments. Inaddition or alternatively, the improved bendability and flexibility ofthe medical device due to the use of the metal alloy can enable themedical device to be more easily inserted into a body passageway. Themetal alloy can also reduce the degree of recoil during the crimpingand/or expansion of the medical device. For example, the medical devicebetter maintains its crimped form and/or better maintains its expandedform after expansion due to the use of the metal alloy. As such, whenthe medical device is to be mounted onto a delivery device when themedical device is crimped, the medical device better maintains itssmaller profile during the insertion of the medical device in a bodypassageway. Also, the medical device better maintains its expandedprofile after expansion so as to facilitate in the success of themedical device in the treatment area. In addition to the improvedphysical properties of the medical device by use of the metal alloy, themetal alloy has improved radiopaque properties as compared to standardmaterials such as stainless steel or cobalt-chromium alloy, thusreducing or eliminating the need for using marker materials on themedical device. For instance, the metal alloy is believed to at leastabout 10-20% more radiopaque than stainless steel or cobalt-chromiumalloy. Specifically, the metal alloy is believed to be at least about33% more radiopaque than cobalt-chromium alloy and is believed to be atleast about 41.5% more radiopaque than stainless steel.

In a further and/or alternative non-limiting aspect of the invention,the medical device can include a bistable construction. In such adesign, the medical device has two or more stable configurations,including a first stable configuration with a first cross-sectionalshape and a second stable configuration with a second cross-sectionalshape. All or a portion of the medical device can include the bistableconstruction. The bistable construction can result in a generallyuniform change in shape of the medical device, or one portion of themedical device can change into one or more configurations and one ormore other portions of the medical device can change into one or moreother configurations.

In still a further and/or alternative aspect of the invention, themedical device can be an expandable device that can be expanded by useof a some other device (e.g., balloon, etc.) and/or is self expanding.The expandable medical device can be at least partially fabricated froma material that has no or substantially no shape memory characteristicsand/or can be at least partially fabricated from a material havingshape-memory characteristics.

In still yet another and/or alternative non-limiting aspect of thepresent invention, the medical device that is at least partially formedfrom the metal alloy can be formed by a variety of manufacturingtechniques. In one non-limiting embodiment of the invention, the medicaldevice can be formed from a rod or tube of the metal alloy. If a solidrod of the metal alloy is formed, the rod can be cut or drilled (e.g.,gun drilled, EDM, etc.) to form a cavity or passageway partially orfully through the rod. The rod or tube can be cleaned, polished,annealed, drawn, etc. to obtain the desired cross-sectional area ordiameter and/or wall thickness of the metal tube. After the metal tubehas been formed to the desired cross-sectional area or diameter and wallthickness, the metal tube can be formed into a medical device by aprocess such as, but not limited to, laser cutting, etching, etc. Afterthe medical device has been formed, the medical device can be cleaned,polished, sterilized, etc. for final processing of the medical device.As can be appreciated, other or additional process steps can be used toat least partially form the medical device from the metal alloy.

In a further and/or alternative non-limiting aspect of the presentinvention, the novel alloy used to at least partially form the medicaldevice is initially formed into a rod or a tube of metal alloy. Themetal alloy rod or tube can be formed by various techniques such as, butnot limited to, 1) melting the metal alloy and/or metals that form themetal alloy (e.g., vacuum arc melting, etc.) and then extruding and/orcasting the metal alloy into a rod or tube, 2) melting the metal alloyand/or metals that form the metal alloy, forming a metal strip and thenrolling and welding the strip into a tube, or 3) consolidating metalpower of the metal alloy and/or metal powder of metals that form themetal alloy. The rod or tube, however formed, generally has a length ofabout 48 inches or less; however, longer lengths can be formed. In onenon-limiting arrangement, the length of the rod or tube is about 8-20inches. The average outer diameter of the rod or tube is generally lessthan about 2 inches (i.e., less than about 3.14 sq. in. cross-sectionalarea), more typically less than about 1 inch outer diameter, and evenmore typically no more than about 0.5 inch outer diameter; however,larger rod or tube diameter sizes can be formed. In one non-limitingconfiguration for a tube, the tube has an inner diameter of about 0.31inch plus or minus about 0.002 inch and an outer diameter of about 0.5inch plus or minus about 0.002 inch. The wall thickness of the tube isabout 0.095 inch plus or minus about 0.002 inch. As can be appreciated,this is just one example of many different sized tubes that can beformed. In one non-limiting process, the rod or tube can be formed fromone or more ingots of metal or metal alloy. In one non-limiting process,an arc melting process (e.g., vacuum arc melting process, etc.) can beused to form the one or more ingots. In another non-limiting process,rhenium powder and molybdenum powder or tungsten and tantalum powder canbe placed in a crucible (e.g., silica crucible, etc.) and heated under acontrolled atmosphere (e.g., vacuum environment, carbon monoxideenvironment, hydrogen and argon environment, helium, argon, etc.) by aninduction melting furnace. It can be appreciated that other oradditional processes can be used to form the one or more ingots. Oncethe ingots are formed, the metal ingots can be cast, extruded through adie, etc. to form the rod or tube. During an extrusion process, theingots are generally heated; however, this is not required. Aclose-fitting rod can be used during the extrusion process to form thetube; however, this is not required. In another and/or additionalnon-limiting process, the tube of the metal alloy can be formed from astrip or sheet of metal alloy. The strip or sheet of metal alloy can beformed into a tube by rolling the edges of the sheet or strip and thenwelding together the edges of the sheet or strip. The welding of theedges of the sheet or strip can be accomplished in several ways such as,but not limited to, a) holding the edges together and then e-beamwelding the edges together in a vacuum, b) positioning a thin strip ofmetal alloy above and/or below the edges of the rolled strip or sheet tobe welded, then welding the one or more strips along the rolled strip orsheet edges, and then grinding off the outer strip, or c) laser weldingthe edges of the rolled sheet or strip in a vacuum, oxygen reducingatmosphere, or inert atmosphere. In still another and/or additionalnon-limiting process, the rod or tube of the metal alloy is formed byconsolidating metal power. In this process, fine particles of molybdenumand rhenium or tungsten and tantalum along with any additives are mixedto form a homogenous blend of particles. Typically the average particlesize of the metal powders is less than about 200 mesh (e.g., less than74 microns). A larger average particle size can interfere with theproper mixing of the metal powders and/or adversely affect one or morephysical properties of the rod or tube formed from the metal powders. Inone non-limiting embodiment, the average particle size of the metalpowders is less than about 230 mesh (e.g., less than 63 microns). Inanother and/or alternative non-limiting embodiment, the average particlesize of the metal powders is about 2-63 microns, and more particularlyabout 5-40 microns. As can be appreciated, smaller average particlesizes can be used. The purity of the metal powders should be selected sothat the metal powders contain very low levels of carbon, oxygen andnitrogen. Typically the carbon content of the molybdenum metal powder isless than about 100 ppm, the oxygen content of the molybdenum metalpowder is less than about 50 ppm, and the nitrogen content of themolybdenum metal powder is less than about 20 ppm. Typically, the carboncontent of the rhenium metal powder is less than about 100 ppm, theoxygen content of the rhenium metal powder is less than about 50 ppm,and the nitrogen content of the rhenium metal powder is less than about20 ppm. Typically, metal powder having a purity grade of at least 99.9and more typically at least about 99.95 should be used to obtain thedesired purity of the powders of molybdenum and rhenium. Similarpurities are desirable for the tungsten and tantalum when forming thetungsten and tantalum alloy. When titanium, yttrium and/or zirconiumpowder is added to the metal powder mixture, the amount of carbon,oxygen and nitrogen in the power should also be minimized. Typically,metal powder having a purity grade of at least 99.8 and more typicallyat least about 99.9 should be used to obtain the desired purity of thepowders of titanium, yttrium and/or zirconium. The blend of metal powderis then pressed together to form a solid solution of the metal alloyinto a rod or tube. Typically the pressing process is by an isostaticprocess(i.e., uniform pressure applied from all sides on the metalpowder). When the metal powders are pressed together isostatically, coldisostatic pressing (CIP) is typically used to consolidate the metalpowders; however, this is not required. The pressing process can bepreformed in an inert atmosphere, an oxygen reducing atmosphere (e.g.,hydrogen, argon and hydrogen mixture, etc.) and/or under a vacuum;however, this is not required. The average density of the rod or tubethat is achieved by pressing together the metal powders is about 80-90%of the final average density of the rod or tube or about 70-96% theminimum theoretical density of the metal alloy. Pressing pressures of atleast about 300 MPa are generally used. Generally the pressing pressureis about 400-700MPa; however, other pressures can be used. After themetal powders are pressed together, the pressed metal powders aresintered at high temperature (e.g., 2000-3000° C.) to fuse the metalpowders together to form the solid metal rod or tube. The sintering ofthe consolidated metal powder can be preformed in an oxygen reducingatmosphere (e.g., helium, argon, hydrogen, argon and hydrogen mixture,etc.) and/or under a vacuum; however, this is not required. At the highsintering temperatures, a high hydrogen atmosphere will reduce both theamount of carbon and oxygen in the formed rod or tube. The sinteredmetal powder generally has an as-sintered average density of about90-99% the minimum theoretical density of the metal alloy. Typically,the sintered rod or tube has a final average density of at least about12 gm/cc, typically at least about 12.5 gm/cc, and more typically about13-14 gm/cc. A rod or tube formed by compressed and sintered metalpowders typically has an average concentricity deviation that is lessthan a rod or tube formed by an arc melting and molding process,extrusion process, or a sheet and welding process; however, this is notalways the situation. Generally, the average concentricity deviation ofthe rod or tube that is formed from compressed and sintered metalpowders is less than about 20%, typically about 1-18%, and moretypically about 1-5%.

In still a further and/or alternative non-limiting aspect of the presentinvention, when a solid rod of the metal alloy is formed, the rod isthen formed into a tube prior to reducing the outer cross-sectional areaor diameter of the rod. The rod can be formed into a tube by a varietyof processes such as, but not limited to, cutting or drilling (e.g., gundrilling, etc.) or by cutting (e.g., EDM, etc.). The cavity orpassageway formed in the rod typically is formed fully through the rod;however, this is not required.

In yet a further and/or alternative non-limiting aspect of the presentinvention, the rod or tube can be cleaned and/or polished after the rodor tube has been form; however, this is not required. Typically the rodor tube is cleaned and/or polished prior to being further processed;however, this is not required. When a rod of the metal alloy is formedinto a tube, the formed tube is typically cleaned and/or polished priorto being further process; however, this is not required. When the rod ortube is resized and/or annealed as discussed in detail below, theresized and/or annealed rod or tube is typically cleaned and/or polishedprior to and/or after each or after a series of resizing and/orannealing processes; however, this is not required. The cleaning and/orpolishing of the rod or tube is used to remove impurities and/orcontaminants from the surfaces of the rod or tube. Impurities andcontaminants can become incorporated into the metal alloy during theprocessing of the rod or tube. The inadvertent incorporation ofimpurities and contaminants in the rod or tube can result in anundesired amount of carbon, nitrogen and/or oxygen, and/or otherimpurities in the metal alloy. The inclusion of impurities andcontaminants in the metal alloy can result in premature micro-crackingof the metal alloy and/or an adverse affect on one or more physicalproperties of the metal alloy (e.g., decrease in tensile elongation,increased ductility, etc.). The cleaning of the metal alloy can beaccomplished by a variety of techniques such as, but not limited to, 1)using a solvent (e.g., acetone, methyl alcohol, etc.) and wiping themetal alloy with a Kimwipe or other appropriate towel, 2) by at leastpartially dipping or immersing the metal alloy in a solvent and thenultrasonically cleaning the metal alloy, and/or 3) by at least partiallydipping or immersing the metal alloy in a pickling solution. As can beappreciated, the metal alloy can be cleaned in other or additional ways.If the metal alloy is to be polished, the metal alloy is generallypolished by use of a polishing solution that typically includes an acidsolution; however, this is not required. In one non-limiting example,the polishing solution includes sulfuric acid; however, other oradditional acids can be used. In one non-limiting polishing solution,the polishing solution can include by volume 60-95% sulfuric acid and5-40% de-ionized water (DI water). Typically, the polishing solutionthat includes an acid will increase in temperature during the making ofthe solution and/or during the polishing procedure. As such, thepolishing solution is typically stirred and/or cooled during making ofthe solution and/or during the polishing procedure. The temperature ofthe polishing solution is typically about 20-100° C., and typicallygreater than about 25° C. One non-limiting polishing technique that canbe used is an electro-polishing technique. When an electro-polishingtechnique is used, a voltage of about 2-30V, and typically about 5-12Vis applied to the rod or tube during the polishing process; however, itwill be appreciated that other voltages can be used. The time used topolish the metal alloy is dependent on both the size of the rod or tubeand the amount of material that needs to be removed from the rod ortube. The rod or tube can be processed by use of a two-step polishingprocess wherein the metal alloy piece is at least partially immersed inthe polishing solution for a given period (e.g., 0.1-15 minutes, etc.),rinsed (e.g., DI water, etc.) for a short period of time (e.g., 0.02-1minute, etc.), and then flipped over and at least partially immersed inthe solution again for the same or similar duration as the first time;however, this is not required. The metal alloy can be rinsed (e.g., DIwater, etc.) for a period of time (e.g., 0.01-5 minutes, etc.) beforerinsing with a solvent (e.g., acetone, methyl alcohol, etc.); however,this is not required. The metal alloy can be dried (e.g., exposure tothe atmosphere, maintained in an inert gas environment, etc.) on a cleansurface. These polishing procedures can be repeated until the desiredamount of polishing of the rod or tube is achieved. The rod or tube canbe uniformly electropolished or selectively electropolished. When therod or tube is selectively electropolished, the selectiveelectropolishing can be used to obtain different surface characteristicsof the rod or tube and/or selectively expose one or more regions of therod or tube; however, this is not required.

In still yet a further and/or alternative non-limiting aspect of thepresent invention, the rod or tube is resized to the desired dimensionof the medical device. In one non-limiting embodiment, thecross-sectional area or diameter of the rod or tube is reduced to afinal rod or tube dimension in a single step or by a series of steps.The reduction of the outer cross-sectional area or diameter of the rodmay be obtained by either centerless grinding, turning,electropolishing, drawing process etc. During the reduction the tube,the outer tube cross-sectional area or diameter, the inner tubecross-sectional area or diameter and/or wall thickness of the tube aretypically reduced; however, this is not required. The outercross-sectional area or diameter size of the rod or tube is typicallyreduced by the use of one or more drawing processes. During the drawingprocess, care should be taken to not form micro-cracks in the rod ortube during the reduction of the rod or tube outer cross-sectional areaor diameter. Generally, the rod or tube should not be reduced incross-sectional area by more about 25% each time the rod or tube isdrawn through a reducing mechanism (e.g., a die, etc.). In onenon-limiting process step, the rod or tube is reduced in cross-sectionalarea by about 0.1-20% each time the rod or tube is drawn through areducing mechanism. In another and/or alternative non-limiting processstep, the rod or tube is reduced in cross-sectional area by about 1-15%each time the rod or tube is drawn through a reducing mechanism. Instill another and/or alternative non-limiting process step, the rod ortube is reduced in cross-sectional area by about 2-15% each time the rodor tube is drawn through reducing mechanism. In yet another onenon-limiting process step, the rod or tube is reduced in cross-sectionalarea by about 5-10% each time the rod or tube is drawn through reducingmechanism. In another and/or alternative non-limiting embodiment of theinvention, the rod or tube of metal alloy is drawn through a die toreduce the cross-sectional area of the rod or tube. Generally, beforedrawing the rod or tube through a die, one end of the rod or tube isnarrowed down (nosed) so as to allow it to be fed through the die;however, this is not required. The tube drawing process is typically acold drawing process or a plug drawing process through a die. When acold drawing or mandrel drawing process is used, a lubricant (e.g.,molybdenum paste, grease, etc.) is typically coated on the outer surfaceof the tube and the tube is then drawn though the die. Typically, littleor no heat is used during the cold drawing process. After the tube hasbeen drawn through the die, the outer surface of the tube is typicallycleaned with a solvent to remove the lubricant so as to limit the amountof impurities that are incorporated in the metal alloy. This colddrawing process can be repeated several times until the desired outercross-sectional area or diameter, inner cross-sectional area or diameterand/or wall thickness of the tube is achieved. A plug drawing processcan also or alternatively be used to size the tube. The plug drawingprocess typically does not use a lubricant during the drawing process.The plug drawing process typically includes a heating step to heat thetube prior and/or during the drawing of the tube through the die. Theelimination of the use of a lubricant can reduce the incidence ofimpurities being introduced into the metal alloy during the drawingprocess. During the plug drawing process, the tube can be protected fromoxygen by use of a vacuum environment, a non-oxygen environment (e.g.,hydrogen, argon and hydrogen mixture, nitrogen, nitrogen and hydrogen,etc.) or an inert environment. One non-limiting protective environmentincludes argon, hydrogen or argon and hydrogen; however, other oradditional inert gasses can be used. As indicated above, the rod or tubeis typically cleaned after each drawing process to remove impuritiesand/or other undesired materials from the surface of the rod or tube;however, this is not required. Typically the rod or tube should beshielded from oxygen and nitrogen when the temperature of the rod ortube is increased to above 500° C., and typically above 450° C., andmore typically above 400° C. When the rod or tube is heated totemperatures above about 400-500° C., the rod or tube has a tendency tobegin form nitrides and/or oxides in the presence of nitrogen andoxygen. In these higher temperature environments, a hydrogenenvironment, argon and hydrogen environment, etc. is generally used.When the rod or tube is drawn at temperatures below 400-500° C., thetube can be exposed to air with little or no adverse affects; however,an inert or slightly reducing environment is generally more desirable.

In still a further and/or alternative non-limiting aspect of the presentinvention, the rod or tube during the drawing process can be nitrided.The nitride layer on the rod or tube can function as a lubricatingsurface during the drawing process to facilitate in the drawing of therod or tube. The rod or tube is generally nitrided in the presence ofnitrogen or a nitrogen mixture (e.g., 97% N-3% H, etc.) for at leastabout 1 minute at a temperature of at least about 400° C. Inone-limiting nitriding process, the rod or tube is heated in thepresence of nitrogen or a nitrogen-hydrogen mixture to a temperature ofabout 400-800° C. for about 1-30 minutes. In one non-limiting embodimentof the invention, the surface of the rod or tube is nitrided prior to atleast one drawing step for the rod or tube. In one non-limiting aspectof this embodiment, the surface of the rod or tube is nitrided prior toa plurality of drawing steps. In another non-limiting aspect of thisinvention, after the rod or tube has been annealed, the rod or tube isnitrided prior to being drawn. In another and/or alternativenon-limiting embodiment, the rod or tube is cleaned to remove nitridecompounds on the surface of the rod or tube prior to annealing the rodto tube. The nitride compounds can be removed by a variety of steps suchas, but not limited to, and grit blasting, polishing, etc. After the rodor tube has been annealed, the rod or tube can be again nitrided priorto one or more drawing steps; however, this is not required. As can beappreciated, the complete outer surface of the tube can be nitrided or aportion of the outer surface of the tube can be nitrided. Nitriding onlyselected portions of the outer surface of the tube can be used to obtaindifferent surface characteristics of the tube; however, this is notrequired.

In yet a further and/or alternative non-limiting aspect of the presentinvention, the rod or tube is cooled after being annealed. Generally therod or tube is cooled at a fairly quickly rate after being annealed soas to inhibit or prevent the formation of a sigma phase in the metalalloy. Generally, the rod or tube is cooled at a rate of at least about50° C. per minute after being annealed, typically at least about 100° C.per minute after being annealed, more typically about 75° -500° C. perminute after being annealed, even more typically about 100° -400° C. perminute after being annealed, still even more typically about 150° -350°C. per minute after being annealed, and yet still more typically about200° -300° C. per minute after being annealed, and still yet even moretypically about 250° -280° C. per minute after being annealed.

In still yet a further and/or alternative non-limiting aspect of thepresent invention, the rod or tube is annealed after one or more drawingprocesses. The metal alloy rod or tube can be annealed after eachdrawing process or after a plurality of drawing processes. The metalalloy rod or tube is typically annealed prior to about a 60%cross-sectional area size reduction of the metal alloy rod or tube. Inother words, the rod or tube should not be reduced in cross-sectionalarea by more than 60% before being annealed. A too large of a reductionin the cross-sectional area of the metal alloy rod or tube during thedrawing process prior to the rod or tube being annealed can result inmicro-cracking of the rod or tube. In one non-limiting processing step,the metal alloy rod or tube is annealed prior to about a 50%cross-sectional area size reduction of the metal alloy rod or tube. Inanother and/or alternative non-limiting processing step, the metal alloyrod or tube is annealed prior to about a 45% cross-sectional area sizereduction of the metal alloy rod or tube. In still another and/oralternative non-limiting processing step, the metal alloy rod or tube isannealed prior to about a 1-45% cross-sectional area size reduction ofthe metal alloy rod or tube. In yet another and/or alternativenon-limiting processing step, the metal alloy rod or tube is annealedprior to about a 5-30% cross-sectional area size reduction of the metalalloy rod or tube. In still yet another and/or alternative non-limitingprocessing step, the metal alloy rod or tube is annealed prior to abouta 5-15% cross-sectional area size reduction of the metal alloy rod ortube. When the rod or tube is annealed, the rod or tube is typicallyheated to a temperature of about 1200-1700° C. for a period of about2-200 minutes; however, other temperatures and/or times can be used. Inone non-limiting processing step, the metal alloy rod or tube isannealed at a temperature of about 1400-1600° C. for about 2-100minutes. In another non-limiting processing step, the metal alloy rod ortube is annealed at a temperature of about 1400-1500° C. for about 5-30minutes. The annealing process typically occurs in an inert environmentor an oxygen reducing environment so as to limit the amount ofimpurities that may embed themselves in the metal alloy during theannealing process. One non-limiting oxygen reducing environment that canbe used during the annealing process is a hydrogen environment; however,it can be appreciated that a vacuum environment can be used or one ormore other or additional gasses can be used to create the oxygenreducing environment. At the annealing temperatures, a hydrogencontaining atmosphere can further reduce the amount of oxygen in the rodor tube. The chamber in which the rod or tube is annealed should besubstantially free of impurities (e.g., carbon, oxygen, and/or nitrogen)so as to limit the amount of impurities that can embed themselves in therod or tube during the annealing process. The annealing chambertypically is formed of a material that will not impart impurities to therod or tube as the rod or tube is being annealed. A non-limitingmaterial that can be used to form the annealing chamber includes, but isnot limited to, molybdenum, rhenium, tungsten, molybdenum TZM alloy,ceramic, etc. When the rod or tube is restrained in the annealingchamber, the restraining apparatuses that are used to contact the metalalloy rod or tube are typically formed of materials that will notintroduce impurities to the metal alloy during the processing of the rodor tube. Non-limiting examples of materials that can be used to at leastpartially form the restraining apparatuses include, but are not limitedto, molybdenum, titanium, yttrium, zirconium, rhenium and/or tungsten.In still another and/or alternative non-limiting processing step, theparameters for annealing can be changed as the tube as thecross-sectional area or diameter; and/or wall thickness of the tube arechanged. It has been found that good grain size characteristics of thetube can be achieved when the annealing parameters are varied as theparameters of the tube change. In one non-limiting processingarrangement, the annealing temperature of the tube having a wallthickness of greater than about 0.015 inch is generally at least about1480° C. for a time period of at least about 5 minutes. In anothernon-limiting processing arrangement, the annealing temperature of thetube having a wall thickness of about 0.008-0.015 inch is generallyabout 1450-1480° C. for a time period of at least about 5 minutes. Inanother non-limiting processing arrangement, the annealing temperatureof the tube having a wall thickness of less than about 0.008 inch isgenerally less than about 1450° C. for a time period of at least about 5minutes. As such, as the wall thickness is reduced, the annealingtemperature is correspondingly reduced; however, the times for annealingcan be increased. As can be appreciated, the annealing temperatures ofthe tube can be decreased as the wall thickness decreases, but theannealing times can remain the same or also be reduced as the wallthickness reduces. After each annealing process, the grain size of themetal in the tube should be no greater than 4 ASTM. Generally the grainsize range is about 4-14 ASTM. Grain sizes of 7-14 ASTM can be achievedby the annealing process of the present invention. It is believed thatas the annealing temperature is reduced as the wall thickness reduces,small grain sizes can be obtained. The grain size of the metal in thetube should be as uniform as possible. In addition, the sigma phase ofthe metal in the tube should be as reduced as much as possible. Thesigma phase is a spherical, elliptical or tetragonal crystalline shapein the metal alloy. The sigma phase is commonly formed of both rheniumand molybdenum, typically with a larger concentration of rhenium. Afterthe final drawing of the tube, a final annealing of the tube can be donefor final strengthening of the tube; however, this is not required. Thisfinal annealing process, when used, generally occurs at a temperature ofabout 1300-1600° C. for at least about 5 minutes; however, othertemperatures and/or time periods can be used.

In another and/or alternative non-limiting aspect of the presentinvention, the rod or tube can be cleaned prior to and/or after beingannealed. The cleaning process is designed to remove impurities,lubricants (e.g., nitride compounds, molybdenum paste, grease, etc.)and/or other materials from the surfaces of the rod or tube. Impuritiesthat are on one or more surfaces of the rod or tube can becomepermanently embedded into the rod or tube during the annealingprocesses. These imbedded impurities can adversely affect the physicalproperties of the metal alloy as the rod or tube is formed into amedical device, and/or can adversely affect the operation and/or life ofthe medical device. In one non-limiting embodiment of the invention, thecleaning process includes a delubrication or degreasing process which istypically followed by pickling process; however, this is not required.The delubrication or degreasing process followed by pickling process aretypically used when a lubricant has been used on the rod or tube duringa drawing process. Lubricants commonly include carbon compounds, nitridecompounds, molybdenum paste, and other types of compounds that canadversely affect the metal alloy if such compounds and/or elements insuch compounds become associated and/or embedded with the metal alloyduring an annealing process. The delubrication or degreasing process canbe accomplished by a variety of techniques such as, but not limitedto, 1) using a solvent (e.g., acetone, methyl alcohol, etc.) and wipingthe metal alloy with a Kimwipe or other appropriate towel, 2) by atleast partially dipping or immersing the metal alloy in a solvent andthen ultrasonically cleaning the metal alloy, 3) sand blasting the metalalloy, and/or 4) chemical etching the metal alloy. As can beappreciated, the metal alloy can be delubricated or degreased in otheror additional ways. After the metal alloy rod or tube has beendelubricated or degreased, the rod or tube can be further cleaned by useof a pickling process; however, this is not required. The picklingprocess, when used, includes the use of one or more acids to removeimpurities from the surface of the rod or tube. Non-limiting examples ofacids that can be used as the pickling solution include, but are notlimited to, nitric acid, acetic acid, sulfuric acid, hydrochloric acid,and/or hydrofluoric acid. These acids are typically analytical reagent(ACS) grade acids. The acid solution and acid concentration are selectedto remove oxides and other impurities on the rod or tube surface withoutdamaging or over etching the surface of the rod or tube. A rod or tubesurface that includes a large amount of oxides and/or nitrides typicallyrequires a stronger pickling solution and/or long picking process times.Non-limiting examples of pickling solutions include 1) 25-60% DI water,30-60% nitric acid, and 2-20% sulfuric acid; 2) 40-75% acetic acid,10-35% nitric acid, and 1-12% hydrofluoric acid; and 3) 50-100%hydrochloric acid. As can be appreciated, one or more different picklingsolutions can be used during the pickling process. During the picklingprocess, the rod or tube is fully or partially immersed in the picklingsolution for a sufficient amount of time to remove the impurities fromthe surface of the rod or tube. Typically, the time period for picklingis about 2-120 seconds; however, other time periods can be used. Afterthe rod or tube has been pickled, the rod or tube is typically rinsedwith a water (e.g., DI water, etc.) and/or a solvent (e.g., acetone,methyl alcohol, etc.) to remove any pickling solution from the rod ortube and then the rod or tube is allowed to dry. The rod or tube may bekeep in a protective environment during the rinse and/or drying processto inhibit or prevent oxides from reforming on the surface of the rod ortube prior to the rod or tube being drawn and/or annealed; however, thisis not required.

In yet another and/or alternative non-limiting aspect of the presentinvention, the restraining apparatuses that are used to contact themetal alloy rod or tube during an annealing process and/or drawingprocess are typically formed of materials that will not introduceimpurities to the metal alloy during the processing of the rod or tube.In one non-limiting embodiment, when the metal alloy rod or tube isexposed to temperatures above 150° C., the materials that contact themetal alloy rod or tube during the processing of the rod or tube aretypically made from molybdenum, rhenium and/or tungsten. When the metalalloy rod or tube is processed at lower temperatures (i.e., 150° C. orless), materials made from Teflon parts can also or alternatively beused.

In still another and/or alternative non-limiting aspect of the presentinvention, the metal alloy rod or tube, after being formed to thedesired outer cross-sectional area or diameter, inner cross-sectionalarea or diameter and/or wall thickness, can be cut and/or etched to atleast partially form the desired configuration of the medical device(e.g., stent, etc.). In one non limiting embodiment of the invention,the metal alloy rod or tube is at least partially cut by a laser. Thelaser is typically desired to have a beam strength which can heat themetal alloy rod or tube to a temperature of at least about 2200-2300° C.In one non-limiting aspect of this embodiment, a pulsed Nd:YAGneodymium-doped yttrium aluminum garnet (Nd:Y₃Al₅O₁₂) or CO₂ laser isused to at least partially cut a pattern of medical device out of themetal alloy rod or tube. In another and/or alternative non-limitingaspect of this embodiment, the cutting of the metal alloy rod or tube bythe laser can occur in a vacuum environment, an oxygen reducingenvironment, or an inert environment; however, this is not required. Ithas been found that laser cutting of the rod or tube in a non-protectedenvironment can result in impurities being introduced into the cut rodor tube, which introduced impurities can induce micro-cracking of therod or tube during the cutting of the rod or tube. One non-limitingoxygen reducing environment includes a combination of argon andhydrogen; however, a vacuum environment, an inert environment, or otheror additional gasses can be used to form the oxygen reducingenvironment. In still another and/or alternative non-limiting aspect ofthis embodiment, the metal alloy rod or tube is stabilized so as tolimit or prevent vibration of the rod or tube during the cuttingprocess. The apparatus used to stabilize the rod or tube can be formedof molybdenum, rhenium, tungsten, molybdenum TZM alloy, ceramic, etc. soas to not introduce contaminants to the rod or tube during the cuttingprocess; however, this is not required. Vibrations in the rod or tubeduring the cutting of the rod or tube can result in the formation ofmicro-cracks in the rod or tube as the rod or tube is cut. The averageamplitude of vibration during the cutting of the rod or tube should beno more than about 150% the wall thickness of the rod or tube. In onenon-limiting aspect of this embodiment, the average amplitude ofvibration should be no more than about 100% the wall thickness of therod or tube. In another non-limiting aspect of this embodiment, theaverage amplitude of vibration should be no more than about 75% the wallthickness of the rod or tube. In still another non-limiting aspect ofthis embodiment, the average amplitude of vibration should be no morethan about 50% the wall thickness of the rod or tube. In yet anothernon-limiting aspect of this embodiment, the average amplitude ofvibration should be no more than about 25% the wall thickness of the rodor tube. In still yet another non-limiting aspect of this embodiment,the average amplitude of vibration should be no more than about 15% thewall thickness of the rod or tube.

In still yet another and/or alternative non-limiting aspect of thepresent invention, the metal alloy rod or tube, after being formed tothe desired medical device, can be cleaned, polished, sterilized,nitrided, etc. for final processing of the medical device. In onenon-limiting embodiment of the invention, the medical device iselectropolished. In one non-limiting aspect of this embodiment, themedical device is cleaned prior to being exposed to the polishingsolution; however, this is not required. The cleaning process, whenused, can be accomplished by a variety of techniques such as, but notlimited to, 1) using a solvent (e.g., acetone, methyl alcohol, etc.) andwiping the medical device with a Kimwipe or other appropriate towel,and/or 2) by at least partially dipping or immersing the medical devicein a solvent and then ultrasonically cleaning the medical device. As canbe appreciated, the medical device can be cleaned in other or additionalways. In another and/or alternative non-limiting aspect of thisembodiment, the polishing solution can include one or more acids. Onenon-limiting formulation of the polishing solution includes about 10-80percent by volume sulfuric acid. As can be appreciated, other polishingsolution compositions can be used. In still another and/or alternativenon-limiting aspect of this embodiment, about 5-12 volts are directed tothe medical device during the electropolishing process; however, othervoltage levels can be used. In yet another and/or alternativenon-limiting aspect of this embodiment, the medical device is rinsedwith water and/or a solvent and allowed to dry to remove polishingsolution on the medical device.

In yet another and/or alternative non-limiting aspect of the presentinvention, the medical device can include, contain and/or be coated withone or more agents that facilitate in the success of the medical deviceand/or treated area. The term “agent” includes, but is not limited to asubstance, pharmaceutical, biologic, veterinary product, drug, andanalogs or derivatives otherwise formulated and/or designed to prevent,inhibit and/or treat one or more clinical and/or biological events,and/or to promote healing. Non-limiting examples of clinical events thatcan be addressed by one or more agents include, but are not limited toviral, fungus and/or bacteria infection; vascular diseases and/ordisorders; digestive diseases and/or disorders; reproductive diseasesand/or disorders; lymphatic diseases and/or disorders; cancer; implantrejection; pain; nausea; swelling; arthritis; bone diseases and/ordisorders; organ failure; immunity diseases and/or disorders;cholesterol problems; blood diseases and/or disorders; lung diseasesand/or disorders; heart diseases and/or disorders; brain diseases and/ordisorders; neuralgia diseases and/or disorders; kidney diseases and/ordisorders; ulcers; liver diseases and/or disorders; intestinal diseasesand/or disorders; gallbladder diseases and/or disorders; pancreaticdiseases and/or disorders; psychological disorders; respiratory diseasesand/or disorders; gland diseases and/or disorders; skin diseases and/ordisorders; hearing diseases and/or disorders; oral diseases and/ordisorders; nasal diseases and/or disorders; eye diseases and/ordisorders; fatigue; genetic diseases and/or disorders; burns; scarringand/or scars; trauma; weight diseases and/or disorders; addictiondiseases and/or disorders; hair loss; cramps; muscle spasms; tissuerepair; nerve repair; neural regeneration and/or the like. Non-limitingexamples of agents that can be used include, but are not limited to,5-Fluorouracil and/or derivatives thereof; 5-Phenylmethimazole and/orderivatives thereof; ACE inhibitors and/or derivatives thereof;acenocoumarol and/or derivatives thereof; acyclovir and/or derivativesthereof; actilyse and/or derivatives thereof; adrenocorticotropichormone and/or derivatives thereof; adriamycin and/or derivativesthereof; agents that modulate intracellular Ca2+ transport such asL-type (e.g., diltiazem, nifedipine, verapamil, etc.) or T-type Ca2+channel blockers (e.g., amiloride, etc.); alpha-adrenergic blockingagents and/or derivatives thereof; alteplase and/or derivatives thereof;amino glycosides and/or derivatives thereof (e.g., gentamycin,tobramycin, etc.); angiopeptin and/or derivatives thereof; angiostaticsteroid and/or derivatives thereof; angiotensin II receptor antagonistsand/or derivatives thereof; anistreplase and/or derivatives thereof;antagonists of vascular epithelial growth factor and/or derivativesthereof; anti-biotics; anti-coagulant compounds and/or derivativesthereof; anti-fibrosis compounds and/or derivatives thereof; antifungalcompounds and/or derivatives thereof; anti-inflammatory compounds and/orderivatives thereof; Anti-Invasive Factor and/or derivatives thereof;anti-metabolite compounds and/or derivatives thereof (e.g.,staurosporin, trichothecenes, and modified diphtheria and ricin toxins,Pseudomonas exotoxin, etc.); anti-matrix compounds and/or derivativesthereof (e.g., colchicine, tamoxifen, etc.); anti-microbial agentsand/or derivatives thereof; anti-migratory agents and/or derivativesthereof (e.g., caffeic acid derivatives, nilvadipine, etc.);anti-mitotic compounds and/or derivatives thereof; anti-neoplasticcompounds and/or derivatives thereof; anti-oxidants and/or derivativesthereof; anti-platelet compounds and/or derivatives thereof;anti-proliferative and/or derivatives thereof; anti-thrombogenic agentsand/or derivatives thereof; argatroban and/or derivatives thereof; ap-1inhibitors and/or derivatives thereof (e.g., for tyrosine kinase,protein kinase C, myosin light chain kinase, Ca2+/calmodulin kinase II,casein kinase II, etc.); aspirin and/or derivatives thereof;azathioprine and/or derivatives thereof; $-Estradiol and/or derivativesthereof; $-1-anticollagenase and/or derivatives thereof; calcium channelblockers and/or derivatives thereof; calmodulin antagonists and/orderivatives thereof (e.g., H7, etc.); CAPTOPRIL and/or derivativesthereof; cartilage-derived inhibitor and/or derivatives thereof; ChIMP-3and/or derivatives thereof; cephalosporin and/or derivatives thereof(e.g., cefadroxil, cefazolin, cefaclor, etc.); chloroquine and/orderivatives thereof; chemotherapeutic compounds and/or derivativesthereof (e.g., 5-fluorouracil, vincristine, vinblastine, cisplatin,doxyrubicin, adriamycin, tamocifen, etc.); chymostatin and/orderivatives thereof; CILAZAPRIL and/or derivatives thereof; clopidigreland/or derivatives thereof; clotrimazole and/or derivatives thereof;colchicine and/or derivatives thereof; cortisone and/or derivativesthereof; coumadin and/or derivatives thereof; curacin-A and/orderivatives thereof; cyclosporine and/or derivatives thereof;cytochalasin and/or derivatives thereof (e.g., cytochalasin A,cytochalasin B, cytochalasin C, cytochalasin D, cytochalasin E,cytochalasin F, cytochalasin G, cytochalasin H, cytochalasin J,cytochalasin K, cytochalasin L, cytochalasin M, cytochalasin N,cytochalasin O, cytochalasin P, cytochalasin Q, cytochalasin R,cytochalasin S, chaetoglobosin A, chaetoglobosin B, chaetoglobosin C,chaetoglobosin D, chaetoglobosin E, chaetoglobosin F, chaetoglobosin G,chaetoglobosin J, chaetoglobosin K, deoxaphomin, proxiphomin,protophomin, zygosporin D, zygosporin E, zygosporin F, zygosporin G,aspochalasin B, aspochalasin C, aspochalasin D, etc.); cytokines and/orderivatives thereof; desirudin and/or derivatives thereof; dexamethazoneand/or derivatives thereof; dipyridamole and/or derivatives thereof;eminase and/or derivatives thereof; endothelin and/or derivativesthereof endothelial growth factor and/or derivatives thereof; epidermalgrowth factor and/or derivatives thereof; epothilone and/or derivativesthereof; estramustine and/or derivatives thereof; estrogen and/orderivatives thereof; fenoprofen and/or derivatives thereof; fluorouraciland/or derivatives thereof; flucytosine and/or derivatives thereof;forskolin and/or derivatives thereof; ganciclovir and/or derivativesthereof; glucocorticoids and/or derivatives thereof (e.g.,dexamethasone, betamethasone, etc.); glycoprotein IIb/IIIa plateletmembrane receptor antibody and/or derivatives thereof; GM-CSF and/orderivatives thereof; griseofulvin and/or derivatives thereof; growthfactors and/or derivatives thereof (e.g., VEGF; TGF; IGF; PDGF; FGF,etc.); growth hormone and/or derivatives thereof; heparin and/orderivatives thereof; hirudin and/or derivatives thereof; hyaluronateand/or derivatives thereof; hydrocortisone and/or derivatives thereof;ibuprofen and/or derivatives thereof; immunosuppressive agents and/orderivatives thereof (e.g., adrenocorticosteroids, cyclosporine, etc.);indomethacin and/or derivatives thereof; inhibitors of thesodium/calcium antiporter and/or derivatives thereof (e.g., amiloride,etc.); inhibitors of the IP3 receptor and/or derivatives thereof;inhibitors of the sodium/hydrogen antiporter and/or derivatives thereof(e.g., amiloride and derivatives thereof, etc.); insulin and/orderivatives thereof; Interferon alpha 2 Macroglobulin and/or derivativesthereof; ketoconazole and/or derivatives thereof; Lepirudin and/orderivatives thereof; LISINOPRIL and/or derivatives thereof; LOVASTATINand/or derivatives thereof; marevan and/or derivatives thereof;mefloquine and/or derivatives thereof; metalloproteinase inhibitorsand/or derivatives thereof; methotrexate and/or derivatives thereof;metronidazole and/or derivatives thereof; miconazole and/or derivativesthereof; monoclonal antibodies and/or derivatives thereof; mutamycinand/or derivatives thereof; naproxen and/or derivatives thereof; nitricoxide and/or derivatives thereof; nitroprusside and/or derivativesthereof; nucleic acid analogues and/or derivatives thereof (e.g.,peptide nucleic acids, etc.); nystatin and/or derivatives thereof;oligonucleotides and/or derivatives thereof; paclitaxel and/orderivatives thereof; penicillin and/or derivatives thereof; pentamidineisethionate and/or derivatives thereof; phenindione and/or derivativesthereof; phenylbutazone and/or derivatives thereof; phosphodiesteraseinhibitors and/or derivatives thereof; Plasminogen Activator Inhibitor-1and/or derivatives thereof; Plasminogen Activator Inhibitor-2 and/orderivatives thereof; Platelet Factor 4 and/or derivatives thereof;platelet derived growth factor and/or derivatives thereof; plavix and/orderivatives thereof; POSTMI 75 and/or derivatives thereof; prednisoneand/or derivatives thereof; prednisolone and/or derivatives thereof;probucol and/or derivatives thereof; progesterone and/or derivativesthereof; prostacyclin and/or derivatives thereof; prostaglandininhibitors and/or derivatives thereof; protamine and/or derivativesthereof; protease and/or derivatives thereof; protein kinase inhibitorsand/or derivatives thereof (e.g., staurosporin, etc.); quinine and/orderivatives thereof; radioactive agents and/or derivatives thereof(e.g., Cu-64, Ca-67, Cs-131, Ga-68, Zr-89, Ku-97, Tc-99m, Rh-105,Pd-103, Pd-109, In-111, I-123, I-125, I-131, Re-186, Re-188, Au-198,Au-199, Pb-203, At-211, Pb-212, Bi-212, H3P32O4, etc.); rapamycin and/orderivatives thereof; receptor antagonists for histamine and/orderivatives thereof; refludan and/or derivatives thereof; retinoic acidsand/or derivatives thereof; revasc and/or derivatives thereof; rifamycinand/or derivatives thereof; sense or anti-sense oligonucleotides and/orderivatives thereof (e.g., DNA, RNA, plasmid DNA, plasmid RNA, etc.);seramin and/or derivatives thereof; steroids; seramin and/or derivativesthereof; serotonin and/or derivatives thereof; serotonin blockers and/orderivatives thereof; streptokinase and/or derivatives thereof;sulfasalazine and/or derivatives thereof; sulfonamides and/orderivatives thereof (e.g., sulfamethoxazole, etc.); sulphated chitinderivatives; Sulphated Polysaccharide Peptidoglycan Complex and/orderivatives thereof; TH1 and/or derivatives thereof (e.g.,Interleukins-2, -12, and -15, gamma interferon, etc.); thioproteseinhibitors and/or derivatives thereof; taxol and/or derivatives thereof(e.g., taxotere, baccatin, 10-deacetyltaxol, 7-xylosyl-10-deacetyltaxol,cephalomannine, 10-deacetyl-7-epitaxol, 7 epitaxol, 10-deacetylbaccatinIII, 10-deacetylcephaolmannine, etc.); ticlid and/or derivativesthereof; ticlopidine and/or derivatives thereof; tick anti-coagulantpeptide and/or derivatives thereof; thioprotese inhibitors and/orderivatives thereof; thyroid hormone and/or derivatives thereof; TissueInhibitor of Metalloproteinase-1 and/or derivatives thereof; TissueInhibitor of Metalloproteinase-2 and/or derivatives thereof; tissueplasma activators; TNF and/or derivatives thereof, tocopherol and/orderivatives thereof; toxins and/or derivatives thereof; tranilast and/orderivatives thereof; transforming growth factors alpha and beta and/orderivatives thereof; trapidil and/or derivatives thereof;triazolopyrimidine and/or derivatives thereof; vapiprost and/orderivatives thereof; vinblastine and/or derivatives thereof; vincristineand/or derivatives thereof; zidovudine and/or derivatives thereof. Ascan be appreciated, the agent can include one or more derivatives of theabove listed compounds and/or other compounds. In one non-limitingembodiment, the agent includes, but is not limited to, trapidil,Trapidil derivatives, taxol, taxol derivatives (e.g., taxotere,baccatin, 10-deacetyltaxol, 7-xylosyl-10-deacetyltaxol, cephalomannine,10-deacetyl-7-epitaxol, 7 epitaxol, 10-deacetylbaccatin III,10-deacetylcephaolmannine, etc.), cytochalasin, cytochalasin derivatives(e.g., cytochalasin A, cytochalasin B, cytochalasin C, cytochalasin D,cytochalasin E, cytochalasin F, cytochalasin G, cytochalasin H,cytochalasin J, cytochalasin K, cytochalasin L, cytochalasin M,cytochalasin N, cytochalasin O, cytochalasin P, cytochalasin Q,cytochalasin R, cytochalasin S, chaetoglobosin A, chaetoglobosin B,chaetoglobosin C, chaetoglobosin D, chaetoglobosin E, chaetoglobosin F,chaetoglobosin G, chaetoglobosin J, chaetoglobosin K, deoxaphomin,proxiphomin, protophomin, zygosporin D, zygosporin E, zygosporin F,zygosporin G, aspochalasin B, aspochalasin C, aspochalasin D, etc.),paclitaxel, paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF(granulo-cytemacrophage colony-stimulating-factor), GM-CSF derivatives,statins or HMG-CoA reductase inhibitors forming a class of hypolipidemicagents, combinations, or analogs thereof, or combinations thereof. Thetype and/or amount of agent included in the device and/or coated on thedevice can vary. When two or more agents are included in and/or coatedon the device, the amount of two or more agents can be the same ordifferent. The type and/or amount of agent included on, in and/or inconjunction with the device are generally selected to address one ormore clinical events. Typically the amount of agent included on, inand/or used in conjunction with the device is about 0.01-100 ug per mm²amd/or at least about 0.01 weight percent of device; however, otheramounts can be used. In one non-limiting embodiment of the invention,the device can be partially of fully coated and/or impregnated with oneor more agents to facilitate in the success of a particular medicalprocedure. The amount of two of more agents on, in and/or used inconjunction with the device can be the same or different. The one ormore agents can be coated on and/or impregnated in the device by avariety of mechanisms such as, but not limited to, spraying (e.g.,atomizing spray techniques, etc.), flame spray coating, powderdeposition, dip coating, flow coating, dip-spin coating, roll coating(direct and reverse), sonication, brushing, plasma deposition,depositing by vapor deposition, MEMS technology, and rotating molddeposition. In another and/or alternative non-limiting embodiment of theinvention, the type and/or amount of agent included on, in and/or inconjunction with the device is generally selected for the treatment ofone or more clinical events. Typically the amount of agent included on,in and/or used in conjunction with the device is about 0.01-100 ug permm² and/or at least about 0.01-100 weight percent of the device;however, other amounts can be used. The amount of two of more agents on,in and/or used in conjunction with the device can be the same ordifferent. For instance, portions of the device to provide local and/orsystemic delivery of one or more agents in and/or to a body passagewayto a) inhibit or prevent thrombosis, in-stent restenosis, vascularnarrowing and/or restenosis after the device has been inserted in and/orconnected to a body passageway, b) at least partially passivate, remove,encapsulate, and/or dissolve lipids, fibroblast, fibrin, etc. in a bodypassageway so as to at least partially remove such materials and/or topassivate such vulnerable materials (e.g., vulnerable plaque, etc.) inthe body passageway in the region of the device and/or downstream of thedevice. As can be appreciated, the one or more agents can have manyother or additional uses. In still another and/or alternativenon-limiting example, the device is coated with and/or includes one ormore agents such as, but not limited to agents associated withthrombolytics, vasodilators, anti-hypertensive agents, antimicrobial oranti-biotic, anti-mitotic, anti-proliferative, anti-secretory agents,non-steroidal anti-inflammatory drugs, immunosuppressive agents, growthfactors and growth factor antagonists, endothelial growth factors andgrowth factor antagonists, antitumor and/or chemotherapeutic agents,anti-polymerases, anti-viral agents, anti-body targeted therapy agents,hormones, anti-oxidants, biologic components, radio-therapeutic agents,radiopaque agents and/or radio-labeled agents. In addition to theseagents, the device can be coated with and/or include one or more agentsthat are capable of inhibiting or preventing any adverse biologicalresponse by and/or to the device that could possibly lead to devicefailure and/or an adverse reaction by human or animal tissue. A widerange of agents thus can be used. The medical device can include,contain and/or be coated with one or more agents that inhibit or preventin-stent restenosis, vascular narrowing, and/or thrombosis during and/orafter the medical device is inserted into a treatment area; however,this is not required. In addition or alternatively, the medical devicecan include, contain and/or be coated with one or more agents that canbe used in conjunction with the one or more agents that inhibit orprevent in-stent restenosis, vascular narrowing, and/or thrombosis thatare included in, contained in and/or coated in the medical device. Assuch, the medical device, when it includes, contains, and/or is coatedwith one or more agents, can include one or more agents to address oneor more medical needs. In one non-limiting embodiment of the invention,the medical device can be partially of fully coated with one or moreagents, impregnated with one or more agents to facilitate in the successof a particular medical procedure. The one or more agents can be coatedon and/or impregnated in the medical device by a variety of mechanismssuch as, but not limited to, spraying (e.g., atomizing spray techniques,etc.), dip coating, roll coating, sonication, brushing, plasmadeposition, depositing by vapor deposition. In another and/oralternative non-limiting embodiment of the invention, the type and/oramount of agent included on, in and/or in conjunction with the medicaldevice is generally selected for the treatment of one or more medicaltreatments. Typically, the amount of agent included on, in and/or usedin conjunction with the medical device is about 0.01-100 ug per mm²;however, other amounts can be used. The amount of two or more agents on,in and/or used in conjunction with the medical device can be the same ordifferent. For instance, one or more agents can be coated on, and/orincorporated in one or more portions of the medical device to providelocal and/or systemic delivery of one or more agents in and/or to a bodypassageway to a) inhibit or prevent thrombosis, in-stent restenosis,vascular narrowing and/or restenosis after the medical device has beeninserted in and/or connected to a body passageway, b) at least partiallypassivate, remove and/or dissolve lipids, fibroblast, fibrin, etc. in abody passageway so as to at least partially remove such materials and/orto passivate such vulnerable materials (e.g., vulnerable plaque, etc.)in the body passageway in the region of the medical device and/or downstream of the medical device. As can be appreciated, the one or moreagents can have many other or additional uses. In another and/oralternative non-limiting example, the medical device is coated withand/or includes one or more agents such as, but not limited to, trapidiland/or trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof. Instill another and/or alternative non-limiting example, the medicaldevice is coated with and/or includes one or more agents such as, butnot limited to trapidil, trapidil derivatives, taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof, and one or more additional agents, such as, butnot limited to, agents associated with thrombolytics, vasodilators,anti-hypertensive agents, anti-microbial or anti-biotic, anti-mitotic,anti-proliferative, anti-secretory agents, non-steroidalanti-inflammatory drugs, immunosuppressive agents, growth factors andgrowth factor antagonists, antitumor and/or chemotherapeutic agents,anti-polymerases, anti-viral agents, anti-body targeted therapy agents,hoimones, anti-oxidants, biologic components, radio-therapeutic agents,radiopaque agents and/or radio-labeled agents. In addition to theseagents, the medical device can be coated with and/or include one or moreagents that are capable of inhibiting or preventing any adversebiological response by and/or to the medical device that could possiblylead to device failure and/or an adverse reaction by human or animaltissue. A wide range of agents thus can be used.

In a further and/or alternative non-limiting aspect of the presentinvention, the one or more agents on and/or in the medical device, whenused on the medical device, can be released in a controlled manner sothe area in question to be treated is provided with the desired dosageof agent over a sustained period of time. As can be appreciated,controlled release of one or more agents on the medical device is notalways required and/or desirable. As such, one or more of the agents onand/or in the medical device can be uncontrollably released from themedical device during and/or after insertion of the medical device inthe treatment area. It can also be appreciated that one or more agentson and/or in the medical device can be controllably released from themedical device and one or more agents on and/or in the medical devicecan be uncontrollably released from the medical device. It can also beappreciated that one or more agents on and/or in one region of themedical device can be controllably released from the medical device andone or more agents on and/or in the medical device can be uncontrollablyreleased from another region on the medical device. As such, the medicaldevice can be designed such that 1) all the agent on and/or in themedical device is controllably released, 2) some of the agent on and/orin the medical device is controllably released and some of the agent onthe medical device is non-controllably released, or 3) none of the agenton and/or in the medical device is controllably released. The medicaldevice can also be designed such that the rate of release of the one ormore agents from the medical device is the same or different. Themedical device can also be designed such that the rate of release of theone or more agents from one or more regions on the medical device is thesame or different. Non-limiting arrangements that can be used to controlthe release of one or more agent from the medical device include a) atleast partially coat one or more agents with one or more polymers, b) atleast partially incorporate and/or at least partially encapsulate one ormore agents into and/or with one or more polymers, and/or c) insert oneor more agents in pores, passageway, cavities, etc. in the medicaldevice and at least partially coat or cover such pores, passageway,cavities, etc. with one or more polymers. As can be appreciated, otheror additional arrangements can be used to control the release of one ormore agent from the medical device. The one or more polymers used to atleast partially control the release of one or more agent from themedical device can be porous or non-porous. The one or more agents canbe inserted into and/or applied to one or more surface structures and/ormicro-structures on the medical device, and/or be used to at leastpartially form one or more surface structures and/or micro-structures onthe medical device. As such, the one or more agents on the medicaldevice can be 1) coated on one or more surface regions of the medicaldevice, 2) inserted and/or impregnated in one or more surface structuresand/or micro-structures, etc. of the medical device, and/or 3) form atleast a portion or be included in at least a portion of the structure ofthe medical device. When the one or more agents are coated on themedical device, the one or more agents can 1) be directly coated on oneor more surfaces of the medical device, 2) be mixed with one or morecoating polymers or other coating materials and then at least partiallycoated on one or more surfaces of the medical device, 3) be at leastpartially coated on the surface of another coating material that hasbeen at least partially coated on the medical device, and/or 4) be atleast partially encapsulated between a) a surface or region of themedical device and one or more other coating materials and/or b) two ormore other coating materials. As can be appreciated, many other coatingarrangements can be additionally or alternatively used. When the one ormore agents are inserted and/or impregnated in one or more internalstructures, surface structures and/or micro-structures of the medicaldevice, 1) one or more other coating materials can be applied at leastpartially over the one or more internal structures, surface structuresand/or micro-structures of the medical device, and/or 2) one or morepolymers can be combined with one or more agents. As such, the one ormore agents can be 1) embedded in the structure of the medical device;2) positioned in one or more internal structures of the medical device;3) encapsulated between two polymer coatings; 4) encapsulated betweenthe base structure and a polymer coating; 5) mixed in the base structureof the medical device that includes at least one polymer coating; or 6)one or more combinations of 1, 2, 3, 4 and/or 5. In addition oralternatively, the one or more coating of the one or more polymers onthe medical device can include 1) one or more coatings of non-porouspolymers; 2) one or more coatings of a combination of one or more porouspolymers and one or more non-porous polymers; 3) one or more coating ofporous polymer, or 4) one or more combinations of options 1, 2, and 3.As can be appreciated different agents can be located in and/or betweendifferent polymer coating layers and/or on and/or the structure of themedical device. As can also be appreciated, many other and/or additionalcoating combinations and/or configurations can be used. Theconcentration of one or more agents, the type of polymer, the typeand/or shape of internal structures in the medical device and/or thecoating thickness of one or more agents can be used to control therelease time, the release rate and/or the dosage amount of one or moreagents; however, other or additional combinations can be used. As such,the agent and polymer system combination and location on the medicaldevice can be numerous. As can also be appreciated, one or more agentscan be deposited on the top surface of the medical device to provide aninitial uncontrolled burst effect of the one or more agents prior to 1)the control release of the one or more agents through one or more layersof polymer system that include one or more non-porous polymers and/or 2)the uncontrolled release of the one or more agents through one or morelayers of polymer system. The one or more agents and/or polymers can becoated on the medical device by a variety of mechanisms such as, but notlimited to, spraying (e.g., atomizing spray techniques, etc.), dipcoating, roll coating, sonication, brushing, plasma deposition, and/ordepositing by vapor deposition. The thickness of each polymer layerand/or layer of agent is generally at least about 0.01 μm and isgenerally less than about 150 μm. In one non-limiting embodiment, thethickness of a polymer layer and/or layer of agent is about 0.02-75 μm,more particularly about 0.05-50 μm, and even more particularly about1-30 μm. When the medical device includes and/or is coated with one ormore agents such that at least one of the agents is at least partiallycontrollably released from the medical device, the need or use ofbody-wide therapy for extended periods of time can be reduced oreliminated. In the past, the use of body-wide therapy was used by thepatient long after the patient left the hospital or other type ofmedical facility. This body-wide therapy could last days, weeks, monthsor sometimes over a year after surgery. The medical device of thepresent invention can be applied or inserted into a treatment areaand 1) merely requires reduced use and/or extended use of body widetherapy after application or insertion of the medical device or 2) doesnot require use and/or extended use of body-wide therapy afterapplication or insertion of the medical device. As can be appreciated,use and/or extended use of body wide therapy can be used afterapplication or insertion of the medical device at the treatment area. Inone non-limiting example, no body-wide therapy is needed after theinsertion of the medical device into a patient. In another and/oralternative non-limiting example, short term use of body-wide therapy isneeded or used after the insertion of the medical device into a patient.Such short term use can be terminated after the release of the patientfrom the hospital or other type of medical facility, or one to two daysor weeks after the release of the patient from the hospital or othertype of medical facility; however, it will be appreciated that othertime periods of body-wide therapy can be used. As a result of the use ofthe medical device of the present invention, the use of body-widetherapy after a medical procedure involving the insertion of a medicaldevice into a treatment area can be significantly reduced or eliminated.

In another and/or alternative non-limiting aspect of the presentinvention, controlled release of one or more agents from the medicaldevice, when controlled release is desired, can be accomplished by usingone or more non-porous polymer layers; however, other and/or additionalmechanisms can be used to controllably release the one or more agents.The one or more agents are at least partially controllably released bymolecular diffusion through the one or more non-porous polymer layers.When one or more non-porous polymer layers are used, the one or morepolymer layers are typically biocompatible polymers; however, this isnot required. The one or more non-porous polymers can be applied to themedical device without the use of chemical, solvents, and/or catalysts;however, this is not required. In one non-limiting example, thenon-porous polymer can be at least partially applied by, but not limitedto, vapor deposition and/or plasma deposition. The non-porous polymercan be selected so as to polymerize and cure merely upon condensationfrom the vapor phase; however, this is not required. The application ofthe one or more non-porous polymer layers can be accomplished withoutincreasing the temperature above ambient temperature (e.g., 65-90° F.);however, this is not required. The non-porous polymer system can bemixed with one or more agents prior to being coated on the medicaldevice and/or be coated on a medical device that previously included oneor more agents; however, this is not required. The use or one or morenon-porous polymer layers allow for accurate controlled release of theagent from the medical device. The controlled release of one or moreagents through the non-porous polymer is at least partially controlledon a molecular level utilizing the motility of diffusion of the agentthrough the non-porous polymer. In one non-limiting example, the one ormore non-porous polymer layers can include, but are not limited to,polyamide, parylene (e.g., parylene C, parylene N) and/or a parylenederivative.

In still another and/or alternative non-limiting aspect of the presentinvention, controlled release of one or more agents from the medicaldevice, when controlled release is desired, can be accomplished by usingone or more polymers that form a chemical bond with one or more agents.In one non-limiting example, at least one agent includes trapidil,trapidil derivative or a salt thereof that is covalently bonded to atleast one polymer such as, but not limited to, an ethylene-acrylic acidcopolymer. The ethylene is the hydrophobic group and acrylic acid is thehydrophilic group. The mole ratio of the ethylene to the acrylic acid inthe copolymer can be used to control the hydrophobicity of thecopolymer. The degree of hydrophobicity of one or more polymers can alsobe used to control the release rate of one or more agents from the oneor more polymers. The amount of agent that can be loaded with one ormore polymers may be a function of the concentration of anionic groupsand/or cationic groups in the one or more polymer. For agents that areanionic, the concentration of agent that can be loaded on the one ormore polymers is generally a function of the concentration of cationicgroups (e.g. amine groups and the like) in the one or more polymer andthe fraction of these cationic groups that can ionically bind to theanionic form of the one or more agents. For agents that are cationic(e.g., trapidil, etc.), the concentration of agent that can be loaded onthe one or more polymers is generally a function of the concentration ofanionic groups (i.e., carboxylate groups, phosphate groups, sulfategroups, and/or other organic anionic groups) in the one or morepolymers, and the fraction of these anionic groups that can ionicallybind to the cationic form of the one or more agents. As such, theconcentration of one or more agent that can be bound to the one or morepolymers can be varied by controlling the amount of hydrophobic andhydrophilic monomer in the one or more polymers, by controlling theefficiency of salt formation between the agent, and/or theanionic/cationic groups in the one or more polymers.

In still another and/or alternative non-limiting aspect of the presentinvention, controlled release of one or more agents from the medicaldevice, when controlled release is desired, can be accomplished by usingone or more polymers that include one or more induced cross-links. Theseone or more cross-links can be used to at least partially control therate of release of the one or more agents from the one or more polymers.The cross-linking in the one or more polymers can be instituted by anumber to techniques such as, but not limited to, using catalysts, usingradiation, using heat, and/or the like. The one or more cross-linksformed in the one or more polymers can result in the one or more agentsto become partially or fully entrapped within the cross-linking, and/orform a bond with the cross-linking. As such, the partially or fullyagent takes longer to release itself from the cross-linking, therebydelaying the release rate of the one or more agents from the one or morepolymers. Consequently, the amount of agent, and/or the rate at whichthe agent is released from the medical device over time can be at leastpartially controlled by the amount or degree of cross-linking in the oneor more polymers.

In still a further and/or alternative aspect of the present invention, avariety of polymers can be coated on the medical device and/or be usedto form at least a portion of the medical device. The one or morepolymers can be used on the medical for a variety of reasons such as,but not limited to, 1) forming a portion of the medical device, 2)improving a physical property of the medical device (e.g., improvestrength, improve durability, improve biocompatibility, reduce friction,etc.), 3) forming a protective coating on one or more surface structureson the medical device, 4) at least partially forming one or more surfacestructures on the medical device, and/or 5) at least partiallycontrolling a release rate of one or more agents from the medicaldevice. As can be appreciated, the one or more polymers can have otheror additional uses on the medical device. The one or more polymers canbe porous, non-porous, biostable, biodegradable (i.e., dissolves,degrades, is absorbed, or any combination thereof in the body), and/orbiocompatible. When the medical device is coated with one or morepolymers, the polymer can include 1) one or more coatings of non-porouspolymers; 2) one or more coatings of a combination of one or more porouspolymers and one or more non-porous polymers; 3) one or more coatings ofone or more porous polymers and one or more coatings of one or morenon-porous polymers; 4) one or more coating of porous polymer, or 5) oneor more combinations of options 1, 2, 3 and 4. The thickness of one ormore of the polymer layers can be the same or different. When one ormore layers of polymer are coated onto at least a portion of the medicaldevice, the one or more coatings can be applied by a variety oftechniques such as, but not limited to, vapor deposition and/or plasmadeposition, spraying, dip-coating, roll coating, sonication,atomization, brushing and/or the like; however, other or additionalcoating techniques can be used. The one or more polymers that can becoated on the medical device and/or used to at least partially form themedical device can be polymers that considered to be biodegradable,bioresorbable, or bioerodable; polymers that are considered to bebiostable; and/or polymers that can be made to be biodegradable and/orbioresorbable with modification. Non-limiting examples ofpolymers thatare considered to be biodegradable, bioresorbable, or bioerodableinclude, but are not limited to, aliphatic polyesters; poly(glycolicacid) and/or copolymers thereof (e.g., poly(glycolide trimethylenecarbonate); poly(caprolactone glycolide)); poly(lactic acid) and/orisomers thereof (e.g., poly-L(lactic acid) and/or poly-D Lactic acid)and/or copolymers thereof (e.g. DL-PLA), with and without additives(e.g. calcium phosphate glass), and/or other copolymers (e.g.poly(caprolactone lactide), poly(lactide glycolide), poly(lactic acidethylene glycol)); poly(ethylene glycol); poly(ethylene glycol)diacrylate; poly(lactide); polyalkylene succinate; polybutylenediglycolate; polyhydroxybutyrate (PHB); polyhydroxyvalerate (PHV);polyhydroxybutyrate/polyhydroxyvalerate copolymer (PHB/PHV);poly(hydroxybutyrate-co-valerate); polyhydroxyalkaoates (PHA);polycaprolactone; poly(caprolactone-polyethylene glycol)copolymer;poly(valerolactone); polyanhydrides; poly(orthoesters) and/or blendswith polyanhydrides; poly(anhydride-co-imide); polycarbonates(aliphatic); poly(hydroxyl-esters); polydioxanone; polyanhydrides;polyanhydride esters; polycyanoacrylates; poly(alkyl 2-cyanoacrylates);poly(amino acids); poly(phosphazenes); poly(propylene fumarate);poly(propylene fumarate-co-ethylene glycol); poly(fumarate anhydrides);fibrinogen; fibrin; gelatin; cellulose and/or cellulose derivativesand/or cellulosic polymers (e.g., cellulose acetate, cellulose acetatebutyrate, cellulose butyrate, cellulose ethers, cellulose nitrate,cellulose propionate, cellophane); chitosan and/or chitosan derivatives(e.g., chitosan NOCC, chitosan NOOC-G); alginate; polysaccharides;starch; amylase; collagen; polycarboxylic acids; poly(ethylester-co-carboxylate carbonate) (and/or other tyrosine derivedpolycarbonates); poly(iminocarbonate); poly(BPA-iminocarbonate);poly(trimethylene carbonate); poly(iminocarbonate-amide) copolymersand/or other pseudo-poly(amino acids); poly(ethylene glycol);poly(ethylene oxide); poly(ethylene oxide)/poly(butylene terephthalate)copolymer; poly(epsilon-caprolactone-dimethyltrimethylene carbonate);poly(ester amide); poly(amino acids) and conventional synthetic polymersthereof; poly(alkylene oxalates); poly(alkylcarbonate); poly(adipicanhydride); nylon copolyamides; NO-carboxymethyl chitosan NOCC);carboxymethyl cellulose; copoly(ether-esters) (e.g., PEO/PLA dextrans);polyketals; biodegradable polyethers; biodegradable polyesters;polydihydropyrans; polydepsipeptides; polyarylates (L-tyrosine-derived)and/or free acid polyarylates; polyamides (e.g., Nylon 66,polycaprolactam); poly(propylene fumarate-co-ethylene glycol) (e.g.,fumarate anhydrides); hyaluronates; poly-p-dioxanone; polypeptides andproteins; polyphosphoester; polyphosphoester urethane; polysaccharides;pseudo-poly(amino acids); starch; terpolymer; (copolymers of glycolide,lactide, or dimethyltrimethylene carbonate); rayon; rayon triacetate;latex; and/pr copolymers, blends, and/or composites of above.Non-limiting examples of polymers that considered to be biostableinclude, but are not limited to, parylene; parylene c; parylene f;parylene n; parylene derivatives; maleic anyhydride polymers;phosphorylcholine; poly n-butyl methacrylate (PBMA);polyethylene-co-vinyl acetate (PEVA); PBMA/PEVA blend or copolymer;polytetrafluoroethene (Teflon®) and derivatives; poly-paraphenyleneterephthalamide (Kevlar®); poly(ether ether ketone) (PEEK);poly(styrene-b-isobutylene-b-styrene) (TransluteTM);tetramethyldisiloxane (side chain or copolymer); polyimidespolysulfides; poly(ethylene terephthalate); poly(methyl methacrylate);poly(ethylene-co-methyl methacrylate); styrene-ethylene/butylene-styreneblock copolymers; ABS; SAN; acrylic polymers and/or copolymers (e.g.,n-butyl-acrylate, n-butyl methacrylate, 2-ethylhexyl acrylate,lauryl-acrylate, 2-hydroxy-propyl acrylate, polyhydroxyethyl,methacrylate/methylmethacrylate copolymers); glycosaminoglycans; alkydresins; elastin; polyether sulfones; epoxy resin; poly(oxymethylene);polyolefins; polymers of silicone; polymers ofmethane; polyisobutylene;ethylene-alphaolefin copolymers; polyethylene; polyacrylonitrile;fluorosilicones; poly(propylene oxide); polyvinyl aromatics (e.g.polystyrene); poly(vinyl ethers) (e.g. polyvinyl methyl ether);poly(vinyl ketones); poly(vinylidene halides) (e.g. polyvinylidenefluoride, polyvinylidene chloride); poly(vinylpyrolidone);poly(vinylpyrolidone)/vinyl acetate copolymer; polyvinylpridineprolastin or silk-elastin polymers (SELP); silicone; silicone rubber;polyurethanes (polycarbonate polyurethanes, silicone urethane polymer)(e.g., chronoflex varieties, bionate varieties); vinyl halide polymersand/or copolymers (e.g. polyvinyl chloride); polyacrylic acid; ethyleneacrylic acid copolymer; ethylene vinyl acetate copolymer; polyvinylalcohol; poly(hydroxyl alkylmethacrylate); Polyvinyl esters (e.g.polyvinyl acetate); and/or copolymers, blends, and/or composites ofabove. Non-limiting examples of polymers that can be made to bebiodegradable and/or bioresorbable with modification include, but arenot limited to, hyaluronic acid (hyanluron); polycarbonates;polyorthocarbonates; copolymers of vinyl monomers; polyacetals;biodegradable polyurethanes; polyacrylamide; polyisocyanates; polyamide;and/or copolymers, blends, and/or composites of above. As can beappreciated, other and/or additional polymers and/or derivatives of oneor more of the above listed polymers can be used. The one or morepolymers can be coated on the medical device by a variety of mechanismssuch as, but not limited to, spraying (e.g., atomizing spray techniques,etc.), dip coating, roll coating, sonication, brushing, plasmadeposition, and/or depositing by vapor deposition. The thickness of eachpolymer layer is generally at least about 0.01 μm and is generally lessthan about 150 μm; however, other thicknesses can be used. In onenon-limiting embodiment, the thickness of a polymer layer and/or layerof agent is about 0.02-75 μm, more particularly about 0.05-50 μm, andeven more particularly about 1-30 μm. As can be appreciated, otherthicknesses can be used. In one non-limiting embodiment, the medicaldevice includes and/or is coated with parylene, PLGA, POE, PGA, PLLA,PAA, PEG, chitosan and/or derivatives of one or more of these polymers.In another and/or alternative non-limiting embodiment, the medicaldevice includes and/or is coated with a non-porous polymer thatincludes, but is not limited to, polyamide, parylene c, parylene nand/or a parylene derivative. In still another and/or alternativenon-limiting embodiment, the medical device includes and/or is coatedwith poly(ethylene oxide), poly(ethylene glycol), and poly(propyleneoxide), polymers of silicone, methane, tetrafluoroethylene (includingTEFLON brand polymers), tetramethyldisiloxane, and the like.

In another and/or alternative non-limiting aspect of the presentinvention, the medical device, when including and/or is coated with oneor more agents, can include and/or can be coated with one or more agentsthat are the same or different in different regions of the medicaldevice and/or have differing amounts and/or concentrations in differingregions of the medical device. For instance, the medical device can a)be coated with and/or include one or more biologicals on at least oneportion of the medical device and at least another portion of themedical device is not coated with and/or includes agent; b) be coatedwith and/or include one or more biologicals on at least one portion ofthe medical device that is different from one or more biologicals on atleast another portion of the medical device; c) be coated with and/orinclude one or more biologicals at a concentration on at least oneportion of the medical device that is different from the concentrationof one or more biologicals on at least another portion of the medicaldevice; etc.

In still another and/or alternative non-limiting aspect of the presentinvention, one or more surfaces of the medical device can be treated toachieve the desired coating properties of the one or more agents and oneor more polymers coated on the medical device. Such surface treatmenttechniques include, but are not limited to, cleaning, buffing,smoothing, etching (chemical etching, plasma etching, etc.), etc. Whenan etching process is used, various gasses can be used for such asurface treatment process such as, but not limited to, carbon dioxide,nitrogen, oxygen, Freon, helium, hydrogen, etc. The plasma etchingprocess can be used to clean the surface of the medical device, changethe surface properties of the medical device so as to affect theadhesion properties, lubricity properties, etc. of the surface of themedical device. As can be appreciated, other or additional surfacetreatment processes can be used prior to the coating of one or moreagents and/or polymers on the surface of the medical device. In onenon-limiting manufacturing process, one or more portions of the medicaldevice are cleaned and/or plasma etched; however, this is not required.Plasma etching can be used to clean the surface of the medical device,and/or to form one or more non-smooth surfaces on the medical device tofacilitate in the adhesion of one or more coatings of agents and/or oneor more coatings of polymer on the medical device. The gas for theplasma etching can include carbon dioxide and/or other gasses. Once oneor more surface regions of the medical device have been treated, one ormore coatings of polymer and/or agent can be applied to one or moreregions of the medical device. For instance, 1) one or more layers ofporous or non-porous polymer can be coated on an outer and/or innersurface of the medical device, 2) one or more layers of agent can becoated on an outer and/or inner surface of the medical device, or 3) oneor more layers of porous or non-porous polymer that includes one or moreagents can be coated on an outer and/or inner surface of the medicaldevice. The one or more layers of agent can be applied to the medicaldevice by a variety of techniques (e.g., dipping, rolling, brushing,spraying, particle atomization, etc.). One non-limiting coatingtechnique is by an ultrasonic mist coating process wherein ultrasonicwaves are used to break up the droplet of agent and form a mist of veryfine droplets. These fine droplets have an average droplet diameter ofabout 0.1-3 microns. The fine droplet mist facilitates in the formationof a uniform coating thickness and can increase the coverage area on themedical device.

In still yet another and/or alternative non-limiting aspect of thepresent invention, one or more portions of the medical device can 1)include the same or different agents, 2) include the same or differentamount of one or more agents, 3) include the same or different polymercoatings, 4) include the same or different coating thicknesses of one ormore polymer coatings, 5) have one or more portions of the medicaldevice controllably release and/or uncontrollably release one or moreagents, and/or 6) have one or more portions of the medical devicecontrollably release one or more agents and one or more portions of themedical device uncontrollably release one or more agents.

In yet another and/or alternative non-limiting aspect of the invention,the medical device can include a marker material that facilitatesenabling the medical device to be properly positioned in a bodypassageway. The marker material is typically designed to be visible toelectromagnetic waves (e.g., x-rays, microwaves, visible light, inferredwaves, ultraviolet waves, etc.); sound waves (e.g., ultrasound waves,etc.); magnetic waves (e.g., MRI, etc.); and/or other types ofelectromagnetic waves (e.g., microwaves, visible light, inferred waves,ultraviolet waves, etc.). In one non-limiting embodiment, the markermaterial is visible to x-rays (i.e., radiopaque). The marker materialcan form all or a portion of the medical device and/or be coated on oneor more portions (flaring portion and/or body portion; at ends ofmedical device; at or near transition of body portion and flaringsection; etc.) of the medical device. The location of the markermaterial can be on one or multiple locations on the medical device. Thesize of the one or more regions that include the marker material can bethe same or different. The marker material can be spaced at defineddistances from one another so as to form ruler like markings on themedical device to facilitate in the positioning of the medical device ina body passageway. The marker material can be a rigid or flexiblematerial. The marker material can be a biostable or biodegradablematerial. When the marker material is a rigid material, the markermaterial is typically formed of a metal material (e.g., metal band,metal plating, etc.); however, other or additional materials can beused. The metal which at least partially forms the medical device canfunction as a marker material; however, this is not required. When themarker material is a flexible material, the marker material typically isformed of one or more polymers that are marker materialsin-of-themselves and/or include one or more metal powders and/or metalcompounds. In one non-limiting embodiment, the flexible marker materialincludes one or more metal powders in combinations with parylene, PLGA,POE, PGA, PLLA, PAA, PEG, chitosan and/or derivatives of one or more ofthese polymers. In another and/or alternative non-limiting embodiment,the flexible marker material includes one or more metals and/or metalpowders of aluminum, barium, bismuth, cobalt, copper, chromium, gold,iron, stainless steel, titanium, vanadium, nickel, zirconium, niobium,lead, molybdenum, platinum, yttrium, calcium, rare earth metals,rhenium, zinc, silver, depleted radioactive elements, tantalum and/ortungsten; and/or compounds thereof The marker material can be coatedwith a polymer protective material; however, this is not required. Whenthe marker material is coated with a polymer protective material, thepolymer coating can be used to 1) at least partially insulate the markermaterial from body fluids, 2) facilitate in retaining the markermaterial on the medical device, 3) at least partially shielding themarker material from damage during a medical procedure and/or 4) providea desired surface profile on the medical device. As can be appreciated,the polymer coating can have other or additional uses. The polymerprotective coating can be a biostable polymer or a biodegradable polymer(e.g., degrades and/or is absorbed). The coating thickness of theprotective coating polymer material, when used, is typically less thanabout 300 microns; however, other thickness can be used. In onenon-limiting embodiment, the protective coating materials includeparylene, PLGA, POE, PGA, PLLA, PAA, PEG, chitosan and/or derivatives ofone or more of these polymers.

In a further and/or alternative non-limiting aspect of the presentinvention, the medical device or one or more regions of the medicaldevice can be constructed by use of one or more microelectromechanicalmanufacturing techniques (MEMS (e.g., micro-machining, lasermicro-machining, laser micro-machining, micro-molding, etc.); however,other or additional manufacturing techniques can be used. The medicaldevice can include one or more surface structures (e.g., pore, channel,pit, rib, slot, notch, bump, teeth, needle, well, hole, groove, etc.).These structures can be at least partially formed by MEMS (e.g.,micro-machining, etc.) technology and/or other types of technology. Themedical device can include one or more micro-structures (e.g.,micro-needle, micro-pore, micro-cylinder, micro-cone, micro-pyramid,micro-tube, micro-parallelopiped, micro-prism, micro-hemisphere, teeth,rib, ridge, ratchet, hinge, zipper, zip-tie like structure, etc.) on thesurface of the medical device. As defined herein, a micro-structure is astructure that has at least one dimension (e.g., average width, averagediameter, average height, average length, average depth, etc.) that isno more than about 2mm, and typically no more than about 1 mm. As can beappreciated, the medical device, when including one or more surfacestructures, a) all the surface structures can be micro-structures, b)all the surface structures can be non-micro-structures, or c) a portionof the surface structures can be micro-structures and a portion can benon-micro-structures. Non-limiting examples of structures that can beformed on the medical devices such as stents are illustrated in UnitedStates Patent Publication Nos. 2004/0093076 and 2004/0093077, which areincorporated herein by reference. Typically, the micro-structures, whenformed, extend from or into the outer surface no more than about 400microns, and more typically less than about 300 microns, and moretypically about 15-250 microns; however, other sizes can be used. Themicro-structures can be clustered together or disbursed throughout thesurface of the medical device. Similar shaped and/or sizedmicro-structures and/or surface structures can be used, or differentshaped and/or sized micro-structures can be used. When one or moresurface structures and/or micro-structures are designed to extend fromthe surface of the medical device, the one or more surface structuresand/or micro-structures can be formed in the extended position and/or bedesigned so as to extend from the medical device during and/or afterdeployment of the medical device in a treatment area. Themicro-structures and/or surface structures can be designed to containand/or be fluidly connected to a passageway, cavity, etc.; however, thisis not required. The one or more surface structures and/ormicro-structures can be used to engage and/or penetrate surroundingtissue or organs once the medical device has be position on and/or in apatient; however, this is not required. The one or more surfacestructures and/or micro-structures can be used to facilitate in formingmaintaining a shape of a medical device (i.e., see devices in UnitedStates Patent Publication Nos. 2004/0093076 and 2004/0093077). The oneor more surface structures and/or micro-structures can be at leastpartially formed by MEMS (e.g., micro-machining, laser micro-machining,micro-molding, etc.) technology; however, this is not required. In onenon-limiting embodiment, the one or more surface structures and/ormicro-structures can be at least partially formed of a agent and/or beformed of a polymer. One or more of the surface structures and/ormicro-structures can include one or more internal passageways that caninclude one or more materials (e.g., agent, polymer, etc.); however,this is not required. The one or more surface structures and/ormicro-structures can be formed by a variety of processes (e.g.,machining, chemical modifications, chemical reactions, MEMS (e.g.,micro-machining, etc.), etching, laser cutting, etc.). The one or morecoatings and/or one or more surface structures and/or micro-structuresof the medical device can be used for a variety of purposes such as, butnot limited to, 1) increasing the bonding and/or adhesion of one or moreagents, adhesives, marker materials and/or polymers to the medicaldevice, 2) changing the appearance or surface characteristics of themedical device, and/or 3) controlling the release rate of one or moreagents. The one or more micro-structures and/or surface structures canbe biostable, biodegradable, etc. One or more regions of the medicaldevice that are at least partially formed by microelectromechanicalmanufacturing techniques can be biostable, biodegradable, etc. Themedical device or one or more regions of the medical device can be atleast partially covered and/or filled with a protective material so toat least partially protect one or more regions of the medical device,and/or one or more micro-structures and/or surface structures on themedical device from damage. One or more regions of the medical device,and/or one or more micro-structures and/or surface structures on themedical device can be damaged when the medical device is 1) packagedand/or stored, 2) unpackaged, 3) connected to and/or other securedand/or placed on another medical device, 4) inserted into a treatmentarea, 5) handled by a user, and/or 6) form a barrier between one or moremicro-structures and/or surface structures and fluids in the bodypassageway. As can be appreciated, the medical device can be damaged inother or additional ways. The protective material can be used to protectthe medical device and one or more micro-structures and/or surfacestructures from such damage. The protective material can include one ormore polymers previously identified above. The protective material canbe 1) biostable and/or biodegradable and/or 2) porous and/or non-porous.In one non-limiting design, the polymer is at least partiallybiodegradable so as to at least partially exposed one or moremicro-structure and/or surface structure to the environment after themedical device has been at least partially inserted into a treatmentarea. In another and/or additional non-limiting design, the protectivematerial includes, but is not limited to, sugar (e.g., glucose,fructose, sucrose, etc.), carbohydrate compound, salt (e.g., NaCl,etc.), parylene, PLGA, POE, PGA, PLLA, PAA, PEG, chitosan and/orderivatives of one or more of these materials; however, other and/oradditional materials can be used. In still another and/or additionalnon-limiting design, the thickness of the protective material isgenerally less than about 300 microns, and typically less than about 150microns; however, other thicknesses can be used. The protective materialcan be coated by one or more mechanisms previously described herein.

In one non-limiting process for manufacturing a medical device inaccordance with the present invention, the process includes thefollowing process steps: 1) forming a metal alloy rod or tube; 2)resizing the rod or tube, 3) cleaning and/or pickling the surface of therod or tube prior to annealing the rod or tube; 4) annealing the rod ortube; and 5) repeating steps 2-4 until the rod or tube has been sized tothe desired size. In another and/or alternative non-limiting process formanufacturing a medical device in accordance with the present invention,the process includes the following process steps: 1) forming a metalalloy rod or tube; 2) resizing the rod or tube by use of a mandreland/or plug drawing process, 3) cleaning and/or pickling the surface ofthe rod or tube prior to annealing the rod or tube; 4) annealing the rodor tube prior to a 60% cross-sectional area size reduction of the rod ortube; 5) repeating steps 2-4 until the rod or tube has been sized to thedesired size; 6) cutting and/or etching the rod or tube to at leastpartially form the medical device; and 7) cleaning and/orelectropolishing the medical device. In still another and/or alternativenon-limiting process for manufacturing a medical device in accordancewith the present invention, the process includes the following processsteps: 1) consolidating metal power of the metal alloy and/or metalpowder of metals that form the metal alloy into a tube; 2) resizing thetube one or more times by use of a plug drawing process, 3) cleaningand/or pickling the surface of the tube after each plug drawing process;4) annealing the tube prior to a 45% cross-sectional area size reductionof the tube; 5) repeating steps 2-4 until the tube has been sized to thedesired size; 6) laser cutting the tube to at least partially form themedical device; and 7) cleaning and/or electropolishing the medicaldevice. As can be appreciated, other or additional process steps can beused to form the medical device from a metal alloy. In each of thenon-limiting processes set forth above, the medical device can befurther processed to include 1) a marker material, 2) one or moretherapeutic agents and/or 3) one or more polymer coatings. The variousmethods for forming the medical device as set forth above can be used toconstruct a tubular structure for used in body passageway, whereby thefinal tubular structure is comprised of smaller tubular structures(i.e., segments) that are affixed to one another other. One or more ofthe smaller tubular structures can be 1) annealed prior to or afterseparation from the initial rod or tube, b) subjected to secondaryfinishing, c) be subjected to secondary forming, d) be affixed to one ormore additional segments that are used to construct the final medicaldevice, e) be subjected to secondary pickling, and/or 1) be subjected toan electropolish processes. As can also be appreciated, each smallertubular structure can have the same or different grain size and/orstructure as compared to one or more other smaller tubular structurethat form the medical device.

The use of the metal alloy to form all or a portion of a medical device(e.g., stent, etc.) results in several advantages over medical devicesformed from other materials. These advantages include, but are notlimited to:

-   -   The metal alloy has increased strength as compared with        stainless steel or chromium-cobalt alloys, thus less quantity of        metal alloy can be used in the medical device to achieve similar        strengths as compared to medical devices formed of different        metals. As such, the resulting medical device can be made        smaller and less bulky by use of the metal alloy without        sacrificing the strength and durability of the medical device.        The medical device can also have a smaller profile, thus can be        inserted into smaller areas, openings and/or passageways. The        increased strength of the metal alloy also results in the        increased radial strength of the medical device. For instance,        the thickness of the walls of the medical device and/or the        wires used to form the medical device can be made thinner and        achieve a similar or improved radial strength as compared with        thicker walled medical devices formed of stainless steel or        cobalt and chromium alloy.    -   The metal alloy has improved stress-strain properties,        bendability properties, elongation properties and/or flexibility        properties of the medical device as compared with stainless        steel or chromium-cobalt alloys, thus resulting in an increase        life for the medical device. For instance, the medical device        can be used in regions that subject the medical device to        repeated bending. Due to the improved physical properties of the        medical device from the metal alloy, the medical device has        improved resistance to fracturing in such frequent bending        environments. These improved physical properties at least in        part result from the composition of the metal alloy; the grain        size of the metal alloy; the carbon, oxygen and nitrogen content        of the metal alloy; and/or the carbon/oxygen ratio of the metal        alloy.    -   The metal alloy has a reduce the degree of recoil during the        crimping and/or expansion of the medical device as compared with        stainless steel or chromium-cobalt alloys. The medical device        formed of the metal alloy better maintains its crimped form        and/or better maintains its expanded form after expansion due to        the use of the metal alloy. As such, when the medical device is        to be mounted onto a delivery device when the medical device is        crimped, the medical device better maintains its smaller profile        during the insertion of the medical device in a body passageway.        Also, the medical device better maintains its expanded profile        after expansion so as to facilitate in the success of the        medical device in the treatment area.    -   The metal alloy has improved radiopaque properties as compared        to standard materials such as stainless steel or cobalt-chromium        alloy, thus reducing or eliminating the need for using marker        materials on the medical device. For instance, the metal alloy        is at least about 10-20% more radiopaque than stainless steel or        cobalt-chromium alloy.    -   The metal alloy is less of an irritant to the body than        stainless steel or cobalt-chromium alloy, thus can result in        reduced inflammation, faster healing, increased success rates of        the medical device. When the medical device is expanded in a        body passageway, some minor damage to the interior of the        passageway can occur. When the body begins to heal such minor        damage, the body has less adverse reaction to the presence of        the metal alloy than compared to other metals such as stainless        steel or cobalt-chromium alloy.

In one specific non-limiting methodology, the tube used to fomi all or aportion of a medical device (e.g., stent, etc.) can be formed from ametal rod which that is gun drilled to form a hollowed tube. The tubecan have a length of about 8-20 inches. The formed tube typically hasrelatively thick walls that are orders of magnitude greater than thewall thickness desired of the tubing for the medical device. As such,the formed tube is drawn down through a die over either a mandrel orplug to reduce the wall thickness of the tube. In the drawing downprocess, the tube can be elongated to a point where it exceeds the limitof the draw bench, at which point if the tubing has still not reachedthe final desired dimensions, will generally be cut (e.g., cut in half,etc.) and then such cut sections are further drawn down until thedesired wall thickness is achieved. Before the tube is drawn through adie, one end of the tube is typically narrowed down(nosed) so as toallow the tube to be fed through the die; however, this is not required.If the tube is cut after being partially drawn down, each of the cuttube section can have one end narrowed down(nosed) so as to allow thecut tube to be fed through the die for further drawing down; however,this is not required. Generally during the drawing down process, thereare several draw steps involved during which the tubing is reduced insize (OD, ID and the wall thickness). The material of the tubinggenerally work hardens after each drawing process. Depending upon thematerial of the tube, the work hardening reduces the ability of thetubing to be drawn down further after a certain number of draw downsthrough a dies. As such, the tube is generally annealed to relieve thework hardened structures of the tube that have formed after being drawndown through a die. The annealing process enables the tube to be furtherdrawn down while reducing the incidence of damage to the tube (cracking,etc.) during the thinning of the walls of the tube. Therefore, the tube,throughout the drawing process, can go through several drawing andannealing steps (e.g, 2-60 drawing and annealing steps, 5-40 drawing andannealing steps, 10-30 drawing and annealing steps, etc.) before thedesired wall thickness of the tubing is achieved. In one non-limitingarrangement, the starting rod can be fabricated by powder metallurgy orarc-melting-extrusion process to form a rod that has a diameter that isclose to that of the final desired OD of the tubing for the medicaldevice. The formed rod can then be subjected to a wire EDM process orgun drilled process to form a tube that has a wall thickness that isslightly greater than the wall thickness of the tubing for the medicaldevice. This formed tube can then be drawn down to a desired wallthickness. In such a drawing down process, 2-10 drawing steps and 1-5annealing steps may be used; however, it will be appreciated that moredrawing and/or annealing steps can be used. The initial length of therod can be selected such that after the tube is formed, the drawing andannealing processes will not cause the tube to elongate beyond theworking limits of the draw bench and hence, the tube will not have to becut and re-nosed; however, this is not required. An alternativeprocessing methodology is to take a conventionally thick starting rodand draw the rod down to a diameter that is close to that of the finaldesired OD of the tubing for the medical device. During the drawing downprocess, 2-10 drawing steps and 1-5 annealing steps may be used;however, it will be appreciated that more drawing and/or annealing stepscan be used. After the rod is drawn down to a desired OD, the rod can besubjected to a wire EDM process or gun drilled process to form a tube.One non-limiting advantage of drawing down the metal rod prior toforming a tube is that a mandrel or plug is not required during thedrawing and/or annealing process, and the inner surface characteristicshave to be monitored of the rod do not have to be monitoring duringdrawing and/or annealing process since the rod does not have a hollowedout interior portion. Still another alternative processing methodologyis to take a conventionally thick starting rod and draw the rod down toa diameter that is larger than the final desired OD of the tubing forthe medical device. During the drawing down process, 2-10 drawing stepsand 1-5 annealing steps may be used; however, it will be appreciatedthat more drawing and/or annealing steps can be used. After the rod isdrawn down to a desired OD, the rod can be subjected to a wire EDMprocess or gun drilled process to form a tube. The formed tube will havedimensions that are slightly larger than that of the final tubing forthe medical device, thus leaving room to further draw the tube to thefinal OD and/or wall thickness. During the further drawing down process,1-10 drawing steps and 0-5 annealing steps may be used; however, it willbe appreciated that more drawing and/or annealing steps can be used.These further tube drawing and/or annealing steps allow for anadjustment in the gain size of the metal tubing and/or enables longertubing to be formed than can be formed by an EDM process or gun drillingprocess. The new process parameters for forming metal tubing inaccordance with the present invention provides a cost effective andquicker method for forming tube for medical devices (e.g, stents, etc.).The process parameters of the present invention are particularly usefulin forming tubing that is made of difficult to form metals such asmolybdenum, titanium, yttrium, zirconium, rhenium, tantalum, and/ortungsten. Conventional drawing tubing for medical devices such as stentsfrom a large tube has several disadvantages and limitations, namely 1) alarge amount of material has to be cored out of the starting rod andthis portion of material is not economically recoverable especially incase of molybdenum, titanium, yttrium, zirconium, rhenium, tantalum,and/or tungsten alloys, 2) each draw step requires either a mandrel or aplug which adds to the cost to the drawing process, 3) due to themandrels and plugs used during the drawing process, there is a lot ofresistance to drawing which can causes extra wear and tear on the diesand the draw bench, 4) additional caution and testing is required ateach step to monitor the inner surface of the tubing since chance offailure and scrap are greater with each additional drawing and/orannealing step, and 5) longer draw benches are required to accommodatethe tubing as it is drawn (The longer the plug and/or the morevariability that is caused due to vibrations and lack of control overpositioning of the plug inside the die can increase incidence of damageduring the forming of the tube. When a mandrel is used, the long themandrel required the more difficult it is to remove from the formed tubewithout damaging the formed tube). These drawbacks are addressed by themethodology of the invention thereby resulting in increased yields andreduced cost during the forming of tubing, especially tubing that isformed of difficult to form metals such as molybdenum, titanium,yttrium, zirconium, rhenium, tantalum, and/or tungsten. For instance, 1)the starting rod of the present invention is either small to begin withor reduced by drawing process. In either case the core material is notlost until a small OD size of the tube is reached, thus loss of materialcored out by a wire EDM process or a gun drilling process is much less,2) plugs or mandrels are not required in most of the processing steps,thereby reducing the cost of tooling and well as less wear and tear onthe drawing equipment, 3) the process of the present invention does notrequire monitoring of the inner surface as extensively as conventionaltube drawing process, thus reducing incidence of scrap and testing time,and/or 4) the tube drawing bench can be as short as 5ft. compared to20+ft. used in conventional drawing process.

In one non-limiting application of the present invention, there isprovided a medical device in the form of a stent that is at leastpartially formed of a metal alloy. The metal alloy imparts one or moreimproved physical characteristics to the medical device (e.g., strength,durability, hardness, biostability, bendability, coefficient offriction, radial strength, flexibility, tensile strength, elongation,longitudinal lengthening, stress-strain properties, improved recoilproperties, radiopacity, heat sensitivity, biocapatability, etc.). Themetal alloy includes at least about 95 weight percent rhenium andmolybdenum or tungsten and tantalum. The medical device can be designedto release one or more agents in a controlled and/or uncontrolledfashion; however, this is not required. For instance, when the medicaldevice includes one or more agents, all of the agents on the medicaldevice can be controllably released from the medical device, all of theagent on the medical device can be uncontrollably released from themedical device, or some of the agent on the medical device can becontrollably released and some uncontrollably released from the medicaldevice. The controlled release of the one or more agents, when used, canbe at least partially accomplished by molecular diffusion through one ormore non-porous polymer layers; however, it will be appreciated thatother, or additional mechanism can be used to control the rate ofrelease of one or more agents from one or more regions of the medicaldevice. The medical device can include one or more layers of polymerand/or agent on the surface structure of one or more regions of themedical device; however, this is not required. The one or more polymers,when used, can include parylene (e.g., parylene C, parylene N), PLGA,POE, PGA, PLLA, PAA, PEG, chitosan and/or derivatives of one or more ofthese polymers; however, other or additional polymers can be used. Manydifferent agents can be used on the medical device. Such agents, whenused, can include, but not limited to, trapidil, trapidil derivatives,taxol, taxol derivatives, cytochalasin, cytochalasin derivatives,paclitaxel, paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof; however, it will be appreciatedthat other or additional agents can be used. The polymer and/or agent,when included on and/or forms a portion of the medical device, can behydrophobic or hydrophilic so as to facilitate in the controlled releaseof the one or more agents; however, this is not required. The thicknessof the one or more polymer layers, when used, can be selected tofacilitate in the controlled release of the one or more agents; however,this is not required. The molecular weight and/or molecular structure ofthe one or more agents and/or one or more polymer can be selected tofacilitate in the release of the one or more agents; however, this isnot required. The medical device can have a variety of applications suchas, but not limited to placement into the vascular system, esophagus,trachea, colon, biliary tract, or urinary tract; however, the medicaldevice can have other applications. The medical device can have one ormore body members, wherein each body member includes first and secondends and a wall surface disposed between the first and second ends. Eachbody member can have a first cross-sectional area which permits deliveryof the body member into a body passageway, and a second, expandedcross-sectional area. The expansion of the medical device body membercan be accomplished in a variety of manners. Typically, the body memberis expanded to its second cross-sectional area by a radially, outwardlyextending force applied at least partially from the interior region ofthe body member (e.g. by use of a balloon, etc.); however, this is notrequired. When the second cross-sectional area is variable, the secondcross-sectional area is typically dependent upon the amount of radiallyoutward force applied to the body member. The medical device can bedesigned such that the body member expands while retaining the originallength of the body member; however, this is not required. The bodymember can have a first cross-sectional shape that is generally circularso as to form a substantially tubular body member; however, the bodymember can have other cross-sectional shapes. When the medical deviceincludes two or more body members, the two or more body members can beconnected together by at least one connector member. The medical devicecan include rounded, smooth and/or blunt surfaces to minimize and/orprevent damage to a body passageway as the medical device is insertedinto a body passageway and/or expanded in a body passageway; however,this is not required. The medical device can be treated with gamma, betaand/or e-beam radiation, and/or otherwise sterilized; however, this isnot required. The medical device can have multiple sections. Thesections of the medical device can have a uniform architecturalconfiguration, or can have differing architectural configurations. Eachof the sections of the medical device can be formed of a single part orformed of multiple parts which have been attached. When a section isformed of multiple parts, typically the section is formed into onecontinuous piece; however, this is not required. As can be appreciated,the medical device can be formed into other devices such as, but notlimited to, an orthopedic device, PFO (patent foramen ovale) device,other types of grafts, guide wide, sheaths, stent catheters,electrophysiology catheters, other type of implant, valve, screw, nail,rod, hypotube, catheter, staple or cutting device, etc. The medicaldevice can include one or more surface structures and/ormicro-structures that include one or more agents, adhesives and/orpolymers; however, this is not required. These structures can be atleast partially formed by MEMS (e.g., micro-machining, etc.) technologyand/or other types of technology. The structures can be designed tocontain and/or fluidly connected to a passageway that includes one ormore agents; however, this is not required. These structures can be usedto engage and/or penetrate surrounding tissue or organs once the medicaldevice has been positioned on and/or in a patient; however, this is notrequired. One or more polymers, adhesives and/or agents can be insertedin these structures and/or at least partially form these structures ofthe medical device; however, this is not required. The structures can beclustered together or disbursed throughout the surface of the medicaldevice. Similar shaped and/or sized surface structures can be used, ordifferent shaped and/or sized structures can be used. The surfacetopography of the medical device can be uniform or vary to achieve thedesired operation and/or agent released from the medical device. As canbe appreciated, the medical device or one or more regions of the medicaldevice can be constructed by use of one or more microelectromechanicalmanufacturing techniques (MEMS (e.g., micro-machining, etc.)); however,this is not required. Materials that can be used by MEMS (e.g.,micro-machining, etc.) technology include, but are not limited to,chitosan, a chitosan derivative, PLGA, a PLGA derivative, PLA, a PLAderivative, PEVA, a PEVA derivative, PBMA, a PBMA derivative, POE, a POEderivative, PGA, a PGA derivative, PLLA, a PLLA derivative, PAA, a PAAderivative, PEG, and chitosan, a chitosan derivative, PLGA, a PLGAderivative, PLA, a PLA derivative, PEVA, a PEVA derivative, PBMA, a PBMAderivative, POE, a POE derivative, PGA, a PGA derivative, PLLA, a PLLAderivative, PAA, a PAA derivative, PEG, a PEG derivative, and/or a PEGderivative. The medical device is typically formed of a biocompatiblematerial. The amount of agent when used on the medical device, can beselected for different medical treatments. Typically, the amount ofagent used in a particular layer of agent or included in a polymer layeris about 0.01-100 ug per mm²; however, other amounts can be used. As canbe appreciated, one or more agents and/or polymers, when used, can beplaced on different regions of the medical device to achieve the desiredoperation and/or agent release from the medical device. The medicaldevice can include one or more coatings of agent on the other surface ofthe medical device to provide a burst of agent to a particular site orregion; however, this is not required. The one or more agents, whenused, can be selected so as to be chemically bonded to one or morepolymers; however, this is not required. The time period the one or moreagents, when used, are released from the medical device can vary.Generally, one or more agents, when used, are released from the medicaldevice for at least several days after the medical device is inserted inthe body of a patient; however, this is not required. One or moreagents, when used, can be released from the medical device for at leastabout one week after the medical device is inserted in the body of apatient, more typically, at least about two weeks after the medicaldevice is inserted in the body of a patient, and even more typically,about one week to one year after the medical device is inserted in thebody of a patient. As can be appreciated, the time frame that one ormore of the agents can be released from the medical device can be longeror shorter. One or more agents, when used, can be released from themedical device controllably released and/or non-controllably released.The time period for the release of two or more agents from the medicaldevice can be the same or different. The type of the one or more agentsused on the medical device, the release rate of the one or more agentsfrom the medical device, and/or the concentration of the one or moreagents being released from the medical device during a certain timeperiod is typically selected to deliver one or more agents directly tothe area of disease after the medical device has been implanted;however, this is not required. In one non-limiting design of medicaldevice, the medical device releases one or more agents over a period oftime after being inserted in the body after the medical device has beenimplanted. In another non-limiting design of medical device, the medicaldevice releases one or more agents over a period of time after beinginserted in the body so that no further drug therapy is required abouttwo weeks to one month after the medical device has been implanted. Inyet another non-limiting design of medical device, the medical devicereleases one or more agents over a period of up to one day after themedical device has been implanted. In still yet another non-limitingdesign of medical device, the medical device releases one or more agentsover a period of up to one week after the medical device has beenimplanted. In a further non-limiting design of medical device, themedical device releases one or more agents over a period of up to twoweeks after the medical device has been implanted. In still a furthernon-limiting design of medical device, the medical device releases oneor more agents over a period of up to one month after the medical devicehas been implanted. In yet a further non-limiting design of medicaldevice, the medical device releases one or more agents over a period ofup to one year after the medical device has been implanted. As can beappreciated, the time or release of one or more agents from the medicaldevice can be more than one year after the medical device has beenimplanted. The use of the medical device can be used in conjunction withother agents not on and/or in the medical device.

One non-limiting object of the present invention is the provision of amethod and process for forming a metal alloy into a medical device.

Another and/or alternative non-limiting object of the present inventionis the provision of a method and process for forming a metal alloy thatinhibits or prevent the formation of micro-cracks during the processingof the alloy into a medical device.

Still another and/or alternative non-limiting object of the presentinvention is the provision of a method and process for forming a metalalloy that inhibits or prevents in the introduction of impurities intothe alloy during the processing of the alloy into a medical device.

Yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device having improvedprocedural success rates.

Still yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that is formed of amaterial that improves the physical properties of the medical device.

Yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that is at leastpartially formed of a metal alloy that has increased strength and canalso be used as a marker material.

Still yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that at least partiallyincludes a metal alloy that enables the medical device to be formed withless material without sacrificing the strength of the medical device ascompared to prior medical devices.

Still yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that is simple and costeffective to manufacture.

A further and/or alternative non-limiting object of the presentinvention is the provision of a medical device that is at leastpartially coated with one or more polymer coatings.

Still a further and/or alternative non-limiting object of the presentinvention is the provision of a medical device that is coated with oneor more agents.

Yet a further and/or alternative non-limiting object of the presentinvention is the provision of a medical device that has one or morepolymer coatings to at least partially control the release rate of oneor more agents.

Still yet a further and/or alternative non-limiting object of thepresent invention is the provision of a medical device that includes oneor more surface structures and/or micro-structures.

Still a further and/or alternative non-limiting object of the presentinvention is the provision of a method and process for forming a metalalloy into a medical device.

Another and/or alternative non-limiting object of the present inventionis the provision of a medical device that includes one or more surfacestructures, micro-structures and/or internal structures and a protectivecoating that at least partially covers and/or protects such structures.

Yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that includes one or moremarkers.

These and other advantages will become apparent to those skilled in theart upon the reading and following of this description taken togetherwith the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Reference may now be made to the drawings, which illustrate variousembodiments that the invention may take in physical form and in certainparts and arrangements of parts wherein:

FIG. 1 is a perspective view of a section of a medical device in theform of an unexpanded stent which permits delivery of the stent into abody passageway; and,

FIG. 2 is one non-limiting process in accordance with the invention formanufacturing a stent from a molybdenum and rhenium alloy or tungstenand tantalum alloy.

DETAILED DESCRIPTION OF THE INVENTION

Referring now to the drawings wherein the showing is for the purpose ofillustrating preferred embodiments of the invention only and not for thepurpose of limiting the same, FIG. 1 discloses a medical device in theform of a stent for use in a body passageway. The stent is particularlyuseful in the cardiovascular field; however, the stent can be used inother medical fields such as, but not limited to, orthopedic field,cardiology field, pulmonology field, urology field, nephrology field,gastrointerology field, gynecology field, otolaryngology field or othersurgical fields. Additionally or alternatively, the medical device isnot limited to a stent, thus can be in the form of many other medicaldevices (e.g., a staple, an orthopedic implant, a valve, a vascularimplant, a pacemaker, a spinal implant, a guide wire, etc.).

The stent, when used for vascular applications, can be used to addressesvarious medical problems such as, but not limited to, restenosis,atherosclerosis, atherogenesis, angina, ischemic disease, congestiveheart failure or pulmonary edema associated with acute myocardialinfarction, atherosclerosis, thrombosis, controlling blood pressure inhypertension, platelet adhesion, platelet aggregation, smooth musclecell proliferation, vascular complications, wounds, myocardialinfarction, pulmonary thromboembolism, cerebral thromboembolism,thrombophlebitis, thrombocytopenia or bleeding disorders.

As illustrated in FIG. 1, stent 20 is in the form of an expandable stentthat includes at least one tubular shaped body member 30 having a firstend 32, a second end 34, and member structures 36 disposed between thefirst and second ends. As can be appreciated, the stent can be formed ofa plurality of body members connected together. Body member 30 has afirst outer cross-sectional area or diameter which permits delivery ofthe body member into a body passageway. The first outer cross-sectionalarea or diameter of the body member is illustrated as substantiallyconstant along the longitudinal length of the body member. As can beappreciated, the body member can have a varying first outercross-sectional area or diameter along at least a portion of thelongitudinal length of the body member. The body member also has asecond expanded outer cross-sectional area or diameter, not shown. Thesecond outer cross-sectional area or diameter typically can vary insize; however, the second outer cross-sectional area or diameter can benon-variable in size. The stent can be expanded in a variety of wayssuch as by a balloon. A balloon expandable stent is typicallypre-mounted or crimped onto an angioplasty balloon catheter. A ballooncatheter is then positioned into the patient via a guide wire. Once thestent is properly positioned, the balloon catheter is inflated to theappropriate pressure for stent expansion. After the stent has beenexpanded, the balloon catheter is deflated and withdrawn, leaving thestent deployed at the treatment area.

One or more surfaces of the stent can be treated so as to have generallysmooth surfaces; however, this is not required. Generally, one or moreends of the stent are treated by filing, buffing, polishing, grinding,coating, and/or the like to remove or reduce the number of rough and/orsharp surfaces; however, this is not required. The smooth surfaces ofthe ends reduce potential damage to surrounding tissue as the stent ispositioned in and/or expanded in a body passageway.

The stent can be at least partially coated with one or more therapeuticagents, not shown. One or more polymers, not shown, can be used inconjunction with the one or more therapeutic agents to 1) facilitate inthe bonding of the one or more therapeutic agents to the stent, and/or2) at least partially control the release of one or more therapeuticagents from the stent.

Referring now to FIG. 2, there is illustrated one non-limiting processfor forming the stent as illustrated in FIG. 1. The stent can be formedof different types of metal alloys. The present invention isparticularly directed to forming all or a portion of a medical devicesuch as a stent from metal alloys that are difficult to work with suchas alloys of molybdenum, titanium, yttrium, zirconium, rhenium,tantalum, and/or tungsten.

The first step to form a stent is to form a tube of a solid solution ofthe metal alloy. When the metal alloy is formed of 1) molybdenum andrhenium alloy, 2) molybdenum and rhenium alloy with small additions ofother metals (e.g., titanium, yttrium, and/or zirconium), 3) tungstenand tantalum, or 4) tungsten and tantalum and small additions of othermetals, the tube that is formed from such metal alloys can be form in avariety of ways in accordance with the present invention. Process step100 illustrates that metal powders of molybdenum and rhenium areselected to form the tube. As will be understood, similar process setsas described below with regard to molybdenum and rhenium alloys and beused to form in tungsten and tantalum alloys. The powders of molybdenumand rhenium constitute a majority weight percent of the materials usedto form the metal tube. As stated above, small amounts of an additionalmetal such as titanium, yttrium and/or zirconium can also be used;however, this is not required. The purity of the metal powders isselected to minimize the carbon, oxygen and nitrogen content in themetal powder. Typically the carbon content of the metal powders is lessthan about 150 ppm, the oxygen content of the metal powders is less thanabout 100 ppm and the nitrogen content of the metal powders is less thanabout 40 ppm.

After the metal powders have been selected, the metal powders aresubstantially homogeneously mixed together as illustrated in processstep 110. After the metal powders are mixed together, the metal powersare isostatically consolidated to form a tube. One non-limitingisostatic consolidation process is a cold isostatic pressing (CIP)process. The isostatic consolidation process typically occurs in avacuum environment (e.g., less than about 1-10⁵ Torr, etc.), an oxygenreducing environment, or in an inert atmosphere. The average density ofthe metal tube obtained by the isostatic consolidation process is about80-90% of the final average density of the tube.

One non-limiting composition of the tube is a solid solution of aboutabout 44-48 weight percent rhenium and about 52-56 weight percentmolybdenum. One non-limiting metal alloy can include about 44.5-47.5weight percent Re and 52.5-55.5 weight percent Mo, a weight percent ofRe plus Mo of at least about 99.9%, and no more than about 0.2 weightimpurities. Another non-limiting composition of the tube is a solidsolution of about 44-48 weight percent rhenium, about 52-56 weightpercent molybdenum, up to about 0.5 weight percent Ti, Y and/or Zr, andno more than about 0.2 weight impurities. One non-limiting metal alloycan include a majority weight percent of Mo and Re and an additionalmetal selected from Ti, Y and/or Zr. One non-limiting metal alloycomposition includes about 44-48 weight percent Re, about 52-56 weightpercent Mo, and up to about 0.5 weight percent Ti, Y and/or Zr. Anothernon-limiting metal alloy composition includes about 44.5-47.5 weightpercent Re, 52.5-55.5 weight percent Mo, a weight percent of Mo plus Replus Ti, Y and/or Zr that is at least about 99.9%, 0.3-0.4 weightpercent Ti, 0.06-0.1 weight percent Zr, 0-0.05 weight percent Y, aweight ratio of Ti:Zr of 1-3:1, and no more than about 0.2 weightimpurities.

After the metal powder has been selected and pressed together, the metalpower is sintered to fuse the metal powders together and to form thetube of metal alloy. The sinter of the metal powders occurs at atemperature of about 2000-2500° C. for about 5-120 minutes; however,other temperatures and/or sintering time can be used. The sintering ofthe metal powder typically takes place in an oxygen reducing environmentto inhibit or prevent impurities from becoming embedded in the metalalloy and/or to further reduce the amount of carbon and/or oxygen in theformed tube. After the sintering process, the tube is formed of a solidsolution of the metal alloy and has an as-sintered average density ofabout 90-99% the minimum theoretical density of the metal alloy.Typically, the sintered tube has a final average density of about 13-14gm/cc. Higher sintering temperatures will generally be required (e.g.,2000-3000° C.) and greater average densities will be obtained (e.g.,greater than 14 gm/cc) when forming tungsten and tantalum alloys. Thelength of the formed tube is typically about 48 inches or less; however,longer lengths can be formed. In one non-limiting arrangement, thelength of the rod or tube is about 8-20 inches. The averageconcentricity deviation of the tube is typically about 1-18%. In onenon-limiting tube configuration, the tube has an inner diameter of about0.31 inch (i.e., 0.0755 sq. in. cross-sectional area) plus or minusabout 0.002 inch and an outer diameter of about 0.5 inch (i.e., 0.1963sq. in. cross-sectional area) plus or minus about 0.002 inch. The wallthickness of the tube is about 0.095 inch plus or minus about 0.002inch. As can be appreciated, this is just one example of many differentsized tubes that can be formed.

In another alternative tube forming process, a rod of metal alloy isfirst formed from one or more ingots of metal alloy. These ingots can beformed by an arc melting process; however, other or additional processcan be used to form the metal ingots. The ingots can be formed into arod by extruding the ingots through a die to form in a rod of a desiredouter cross-sectional area or diameter. The length of the formed rod istypically about 48 inches or less; however, longer lengths can beformed. In one non-limiting arrangement, the length of the rod or tubeis about 8-20 inches. After the rod is formed, the rod is hollowed byEDM to form a tube. The inner cross-sectional area or diameter of thehollowed tube is carved to the exact inner cross-sectional area ordiameter by a wire EDM process. As can be appreciated, the rod can bedrawn down to an intermediate size, and then hollowed by EDM to a tube,and then further drawn down to a desired size. In one non-limiting tubeconfiguration, the tube has an inner diameter of about 0.2-0.4 inch plusor minus about 0.005 inch and an outer diameter of about 0.4-0.6 inchplus or minus about 0.005 inch. The wall thickness of the tube is about0.001-0.15 inch, and generally about 0.001-0.1 inch, and typically about0.04-0.1 inch plus or minus about 0.005 inch. As can be appreciated,this is just one example of many different sized tubes that can beformed.

After the tube is formed, the tube can be drawn down to a desired ODand/or wall thickness. When the tube is drawn down, the annealingtemperature and time is generally adjusted based on the wall thicknessof the tube. For example, the annealing temperature for a molybdenum andrhenium alloy should be about 1500° C. for 30 minutes for drawn tubeswith wall thickness from 0.050″ to 0.015″, 1475° C. for 30 minutes fordrawn tubes with wall thickness from 0.015″ to 0.080″, and about 1425°C. for 30 minutes for drawn tubes with wall thickness from 0.005 to0.002″. Slight differences in temperature and/or annealing times may beused for tungsten and tantalum alloys. The annealing temperature isgenerally reduced for thinner walls in order to obtain a smaller grainstructure for the tubing. The annealing process generally takes place ina hydrogen atmosphere or in a vacuum. After each annealing process, thegrain size of the tubing should be no greater than about an ASTM grainnumber 6, and typically no greater than an ASTM grain number of 8. Afinal grain size of the tube can be up to an ASTM grain number of 14.The grain size in the final tube should be generally uniform, with aminimum amount of sigma phase, which sigma phase has a generallyspherical, elliptical or tetragonal shape. When the tubing is formedprimarily of molybdenum and rhenium, the sigma phase is generally madeup of both rhenium and molybdenum, with heavier concentration ofrhenium.

The tube can be cleaned and/or polished after the tube has been formed;however, this is not required. The cleaning and/or polishing of the tubeis used to remove impurities and/or contaminants from the surfaces ofthe tube and/or to remove rough areas from the surface of the tube.Impurities and contaminants (e.g., carbon, oxygen, etc.) can becomeincorporated into the metal alloy during the processing of the tube. Theinclusion of impurities and contaminants in the metal alloy can resultin premature micro-cracking of the metal alloy and/or the adverse affecton one or more physical properties of the metal alloy. The cleaning ofthe tube can be accomplished by a variety of techniques such as, but notlimited to, 1) using a solvent (e.g., acetone, methyl alcohol, etc.) andwiping the metal alloy with a Kimwipe or other appropriate towel, and/or2) by at least partially dipping or immersing the metal alloy in asolvent and then ultrasonically cleaning the metal alloy. As can beappreciated, the tube can be cleaned in other or additional ways. Thetube, when polished, is generally polished by use of a polishingsolution that typically includes an acid solution; however, this is notrequired. In one non-limiting example, the polishing solution includessulfuric acid; however, other or additional acids can be used. In onenon-limiting polishing solution, the polishing solution can include byvolume 60-95% sulfuric acid and 5-40% de-ionized water (DI water). Thepolishing solution can be increased in temperature during the making ofthe solution and/or during the polishing procedure. One non-limitingpolishing technique that can be used is an electro-polishing technique.The time used to polish the metal alloy is dependent on both the size ofthe tube and the amount of material that needs to be removed from thetube. The tube can be processed by use of a two-step polishing processwherein the metal alloy piece is at least partially immersed in thepolishing solution for a given period (e.g., 0.1-15 minutes, etc.),rinsed (e.g., DI water, etc.) for a short period of time (e.g., 0.02-1minute, etc.), and then flipped over and at least partially immersed inthe solution again for the same or similar duration as the first time;however, this is not required. The tube can be rinsed (e.g., DI water,etc.) for a period of time (e.g., 0.01-5 minutes, etc.) before rinsingwith a solvent (e.g., acetone, methyl alcohol, etc.); however, this isnot required. The tube can be dried (e.g., exposure to the atmosphere,maintained in an inert gas environment, etc.) on a clean surface. Thesepolishing procedures can be repeated until the desired amount ofpolishing of the tube is achieved. Typically, after the tube has beenfirst formed and/or hollowed out, the inner surface (i.e., the innerpassageway of the tube) and the outer surface of the tube are polished.The polishing techniques for the inner and outer surfaces of the tubecan be the same or different. The inner surface and/or outer surface ofthe tube is also typically polished at least after one drawing process.As can be appreciated, the inner and/or outer surface of the tube can bepolished after each drawing process, and/or prior to each annealingprocess. A slurry honing polishing process can be used to polishing theinner and/or outer surface of the tube; however, other or additionalprocesses can be used.

After the tube has been formed (e.g., sintering process, extrusionprocess, etc.), and optionally cleaned, the tube is then drawn through adie one or more times to reduce the inner and outer cross-sectional areaor diameter of the tube and the wall thickness of the tube to thedesired size. As illustrated in process step 130, the tube is reduced insize by the use of a drawing process such as, but not limited to a plugdrawing process. During the drawing process, the tube is heated. Duringthe drawing process, the tube can be protected in a reduced oxygenenvironment such as, but not limited to, an oxygen reducing environment,or inert environment. One non-limiting oxygen reducing environmentincludes argon and about 1-10 volume percent hydrogen. When thetemperature of the drawing process is less than about 400-450° C., theneed to protect the tube from oxygen is significantly diminished. Assuch, a drawing process that occurs at a temperature below about400-450° C. can occur in air. At higher temperatures, the tube is drawnin an oxygen reducing environment or an environment. Typically thedrawing temperature does not exceed about 500-550° C. A mandrel removalprocess can be used during the drawing process for the tube to improvethe shape and/or uniformity of the drawn tube; however, this is notrequired. The amount of outer cross-sectional area or diameter draw downof the tube each time the tube is plug drawn is typically no more thanabout 10-20%. Controlling the degree of draw down facilitates inpreventing the formation of micro-cracks during the drawing process.After each drawing process, the tube can be cleaned; however, this isnot required. During the drawing process, the inner surface of the tubecan be at least partially filled with a close-fitting rod. When aclose-fitting rod is used, the metal rod is inserted into the tube priorto the tube being drawn through a die. The close-fitting rod isgenerally facilitates in maintaining a uniform shape and size of thetube during a drawing process. The close-fitting rod is generally anunalloyed metal rod; however, this is not required. Non-limitingexamples of metals that can be used to form the close-fitting rod aretantalum and niobium. When a close-fitting rod is used, theclose-fitting rod can be used for each drawing process or for selecteddrawing processes. Prior to the high temperature annealing of the tube,the close-fitting rod, when used, it removed from the tube. The tube canbe heated to facilitate in the removal of the close-fitting rod from thetube; however, this is not required. When the tube is heated to removethe close-fitting rod, the tube is generally no heated above about 1000°C., and typically about 600-800° C.; however, other temperatures can beused. When the tube is heated above about 400-450° C., a vacuum, anoxygen reducing environment or an inert environment is generally used toshield the tube from the atmosphere. As can also be appreciated, aclose-fitting tube can also or alternatively be used during theformation of the tube during an extrusion process. Generally after theclose-fitting rod is removed from the tube, the inner and/or outersurface of the tube is polished; however, this is not required.

The tube is typically exposed to a nitriding step prior to drawing downthe tube. The layer of nitride compound that forms on the surface of thetube after a nitriding process has been found to function as alubricating layer for the tube as the tube is drawn down to a smallercross-sectional area or diameter. The nitriding process occurs in anitrogen containing atmosphere at temperatures exceeding 400° C.Typically the nitriding process is about 5-15 minutes at a temperatureof about 450-600° C. The nitrogen atmosphere can be an essentially purenitrogen atmosphere, a nitrogen-hydrogen mixture, etc.

Prior to the tube being drawn down more than about 35-45% from itsoriginal outer cross-sectional area or diameter after the sinteringprocess, the tube is annealed as illustrated in process step 150. If thetube is to be further drawn down after being initially annealed, asubsequent annealing process should be completed prior to the outercross-sectional area or diameter of the tube being drawn down more thanabout 35-45% since a previous annealing process. As such, the tubeshould also be annealed at least once prior to the tube outercross-sectional area or diameter being drawn down more than about 35-45%since being originally sintered or being previously annealed. Thiscontrolled annealing facilitates in preventing the formation ofmicro-cracks during the drawing process. The annealing process of thetube typically takes place in a vacuum environment, an inert atmosphere,or an oxygen reducing environment (e.g., hydrogen, argon, argon and1-10% hydrogen, etc.) at a temperature of about 1400-1600° C. for aperiod of about 5-60 minutes; however, other temperatures and/or timescan be used. The use of an oxygen reducing environment during theannealing process can be used to reduce the amount of oxygen in thetube. The chamber in which the tube is annealed should be substantiallyfree of impurities such as, but not limited to, carbon, oxygen, and/ornitrogen. The annealing chamber typically is formed of a material thatwill not impart impurities to the tube as the tube is being annealed.One non-limiting material that can be used to form the annealing chamberis a molybdenum TZM alloy. The parameters for annealing the tube as thecross-sectional area or diameter and thickness of the tube is changedduring the drawing process can remain constant or be varied. It has beenfound that good grain size characteristics of the tube can be achievedwhen the annealing parameters are varied during the drawing process. Inone non-limiting processing arrangement, the annealing temperature ofthe tube having a wall thickness of about 0.015-0.05 inch is generallyabout 1480-1520° C. for a time period of about 5-40 minutes. In anothernon-limiting processing arrangement, the annealing temperature of thetube having a wall thickness of about 0.008-0.015 inch is generallyabout 1450-1480° C. for a time period of about 5-60 minutes. In anothernon-limiting processing arrangement, the annealing temperature of thetube having a wall thickness of about 0.002-0.008 inch is generallyabout 1400-1450° C. for a time period of about 15-75 minutes. As such,as the wall thickness is reduced, the annealing temperature iscorrespondingly reduced; however, the times for annealing can beincreased. As can be appreciated, the annealing temperatures of the tubecan be decreased as the wall thickness decreases, but the annealingtimes can remain the same or also be reduced as the wall thicknessreduces. After each annealing process, the grain size of the metal inthe tube should be no greater than 4 ASTM, typically no greater than 6ASTM, more typically no greater than 7 ASTM, and even more typically nogreater than about 7.5 ASTM. Grain sizes of 7-14 ASTM can be achieved bythe annealing process of the present invention. It is believed that asthe annealing temperature is reduced as the wall thickness reduces,small grain sizes can be obtained. The grain size of the metal in thetube should be as uniform as possible. In addition, the sigma phase ofthe metal in the tube should be as reduced as much as possible. Thesigma phase is a spherical, elliptical or tetragonal crystalline shapein the metal alloy. The sigma phase is commonly formed of both rheniumand molybdenum, typically with a larger concentration of rhenium. Afterthe final drawing of the tube, a final annealing of the tube can be donefor final strengthening of the tube; however, this is not required. Thisfinal annealing process, when used, generally occurs at a temperature ofabout 1425-1500° C. for about 20-40 minutes; however, other temperaturesand/or time periods can be used. The grain structure can be alteredusing the final anneal process.

After each anneal process, the tube is typically cooled at a fairlyquick rate so as to inhibit or prevent sigma phase formations in themetal alloy. Typically the tube is cooled at a rate of about 100°C.-400° C. per minute, and more typically about 200° C.-300° C. perminute. The tube is can be cooled in a variety of ways (e.g., subjectingthe annealed tube to a cooling gas and/or cooling liquid, placing theannealed tube in a refrigerated environment, etc.).

Prior to each annealing process, the tube is typically cleaned and/orpickled to remove oxides and/or other impurities from the surface of thetube as illustrated in process step 140. Typically the tube is cleanedby first using a solvent (e.g., acetone, methyl alcohol, etc.) andwiping the metal alloy with a Kimwipe or other appropriate towel, and/orby at least partially dipping or immersing the tube in a solvent andthen ultrasonically cleaning the metal alloy. As can be appreciated, thetube can be cleaned other and/or additional ways. After the tube hasbeen cleaned by use of a solvent, the tube is typically further cleanedby use of a pickling process. The pickling process includes the use ofone or more acids to remove impurities from the surface of the tube.Non-limiting examples of acids that can be used as the pickling solutioninclude, but are not limited to, nitric acid, acetic acid, sulfuricacid, hydrochloric acid, and/or hydrofluoric acid. The acid solution andacid concentration and time of pickling are selected to remove oxidesand other impurities on the tube surface without damaging or overetching the surface of the tube. During the pickling process, the tubeis fully or partially immersed in the pickling solution for a sufficientamount of time to remove the impurities from the surface of the tube.After the tube has been pickled, the tube is typically rinsed with asolvent (e.g., acetone, methyl alcohol, etc.) to remove any picklingsolution from the tube and then the tube is allowed to dry. The cleaningof the tube prior to the tube being annealed removes impurities and/orother materials from the surfaces of the tube that could becomepermanently embedded into the tubing during the annealing processes.These imbedded impurities could adversely affect the physical propertiesof the metal alloy as the tube is formed into a medical device, and/orcan adversely affect the operation and/or life of the medical device. Ascan be appreciated, the tube can be again clean and/or pickled afterbeing annealed and prior to be drawn down in the plug drawing process;however, this is not required.

Process steps 130-150 can be repeated as necessary until the tube isdrawn down to the desired size. In one non-limiting process, a tube thatis originally formed after being sintered has an inner diameter of about0.31 inch plus or minus about 0.002 inch, an outer diameter of about 0.5inch plus or minus about 0.002 inch, and a wall thickness of about 0.095inch plus or minus about 0.002 inch. After the tube has been fully drawndown, the tube has an outer diameter of about 0.070 inch, a wallthickness of about 0.0021-0.00362 inch, and the average concentricitydeviation of less than about 10%. Such small sizes for stents which canbe successfully used in a vascular system have heretofore not beenpossible when formed by other types of metal alloys. Typically the wallthickness of stent had to be at least about 0.0027-0.003 inch, or thestent would not have sufficient radial force to maintain the stent in anexpanded state after being expanded. The metal alloy of the presentinvention is believed to be able to have a wall thickness of as small asabout 0.0015 inch and still have sufficient radial force to maintain astent in an expanded state after being expanded. As such, when a tube isformed into a stent, the wall thickness of the tube can be drawn down toless than about 0.0027 inch to form a stent. As can be appreciated, thisis just one example of many different sized tubes that can be formed bythe process of the present invention.

Once the tube has been drawn down to its final size, the tube istypically cleaned (Process Step 140), annealed (Process Step 150) andthen again cleaned (Process Step 160). The cleaning step of process step160 can include merely solvent cleaning, or can also include pickling.

After the tube has been cleaned in process step 160, the tube is thencut into the form of a stent as illustrated in FIG. 1. As can beappreciated, other stent designs can be formed during the cuttingprocess as set forth in process step 170. The cutting of the tube istypically conducted by a laser. The laser that is used to cut the tubeis selected so that has a beam strength used to heat the tube can obtaina cutting temperature of at least about 2350° C. Non-limiting examplesof lasers that can be used include a pulsed Nd:YAG neodymium-dopedyttrium aluminum garnet (Nd:Y₃Al₅O₁₂) or CO₂ laser. The cutting of thetube by the laser occurs in an oxygen reducing environment such as anargon and 1-10 percent by volume hydrogen environment; however, a vacuumenvironment, an inert environment, or another type of oxygen reducingenvironment can be used. During the cutting of the tube, the tube istypically stabilized so as to inhibit or prevent vibration of the tubeduring the cutting process, which vibrations can result in the formationof micro-cracks in the tube as the tube is cut. The tube is typicallystabilized by an apparatus formed of molybdenum, rhenium, tungsten,molybdenum TZM alloy, ceramic, etc. so as to not introduce contaminatesto the tube during the cutting process; however, this is not required.The average amplitude of vibration during the cutting of the tube istypically no more than about 50% the wall thickness of the tube. Assuch, for a tube having a wall thickness of about 0.0024 inch, theaverage amplitude of vibration of the tube during the cutting process isno more than about 0.0012 inch.

The various methods for forming the medical device as set forth abovecan be used to construct a tubular structure for used in bodypassageway, whereby the final tubular structure is comprised of smallertubular structures (i.e., segments) that are affixed to one anotherother. One or more of the smaller tubular structures can be 1) annealedprior to or after separation from the initial rod or tube, b) subjectedto secondary finishing, c) be subjected to secondary forming, d) beaffixed to one or more additional segments that are used to constructthe final medical device, e) be subjected to secondary pickling, and/orf) be subjected to an electropolish processes. As can also beappreciated, each smaller tubular structure can have the same ordifferent grain size and/or structure as compared to one or more othersmaller tubular structure that form the medical device. The formed stenttypically has a tensile elongation of about 25-35%, an average densityof about 13.4-14 gm/cc., an average yield strength of at least about 100(ksi), an average ultimate tensile strength of about 150-310 UTS (ksi),and an average Vickers hardness of 372-653 (i.e., an average Rockwell AHardness of about 70-80 at 77° F., an average Rockwell C Hardness ofabout 39-58 at 77° F. The solid or homogeneous solution of the metalalloy that is used to form the stent has the unique characteristics ofpurity, ductility, grain size, tensile elongation, yield strength andultimate tensile strength that permits 1) the metal alloy to befabricated into the stent from the tube without creating microcrackswhich are detrimental to the stent properties, and 2) the manufacture ofa stent that has improved physical properties over stents formed fromdifferent materials.

After the stent has been cut, the stent can be further processed;however, this is not required. The one or more processes can include,but are not limited to, 1) electropolishing the stent, 2) treating oneor more surfaces of the stent to created generally smooth surfacesand/or other types of surfaces (e.g., filing, buffing, polishing,grinding, coating, nitriding, etc.), 3) at least partially coating thestent with one or more therapeutic agents, 4) at least partially coatingthe stent with one or more polymers, 5) forming one or more surfacestructures and/or micro-structures on one or more portions of the stent,6) inserting one or more markers on one or more portions of the stent,and/or 7) straightening process for the stent. For instance, the stentcan be nitrided to obtain differing surface characteristics of the stentand/or to inhibit oxidation of the surface of the stent; however, thisis not required. The stent can be electropolished to fully orselectively expose one or more surface regions of the stent; however,this is not required. The stent is typically straightened in a rollstraightener and/or other type of device to obtain the designed shape ofthe stent; however, this is not required. After the stent has beenstraightened, the stent can be centerless ground to obtain the desireddimensions of the stent; however, this is not required. The stent can bepolished after the grinding process; however, this is not required.

The process for forming the metal alloy in accordance with the presentinvention is designed to produce structures for medical devices such as,but not limited to metal tubing for stents, that has been in the pastdifficult to achieve when such metal alloys are formed of molybdenum,titanium, yttrium, zirconium, rhenium, tantalum, and/or tungsten. Inaddition, the process of forming the metal alloys into variousstructures in accordance with the present invention limits impurityintroduction into the worked metal alloy, which impurities create orresult in flaws in the metal alloy thereby making such formed structureunacceptable for use in the medical device. It has been found that aunique combination of carbon and oxygen redistributes the oxygen at thegrain boundary of the metal alloy formed of molybdenum, titanium,yttrium, zirconium, rhenium, tantalum, and/or tungsten, which in turnhelps in reducing microcracks(defects) in the ultimately formed medicaldevice. A controlled carbon to oxygen atomic ratio can also be used toobtain a high ductility of the metal alloy which can be measured in partas tensile elongation. An increase in tensile elongation is an importantattribute when forming the metal alloy into various types of medicaldevice (e.g. stent, etc.). Prior art metal forming processes did notaddress the problems associated with obtaining a desired carbon tooxygen atomic ratio in the formed and worked metal alloy. The purity ofthe metal alloy also results in a substantially uniform densitythroughout the metal alloy. The density of the solid homogeneoussolution of the metal alloy results in the high radiopacity of the metalalloy, especially when the metal alloy is formed of molybdenum,titanium, yttrium, zirconium, rhenium, tantalum, and/or tungsten. Whenthe metal alloy is formed of molybdenum and rhenium, the addition ofrhenium in the metal alloy improves the ductility of the molybdenum. Iftitanium, yttrium and/or zirconium are added to the molybdenum andrhenium alloy, the titanium, yttrium and/or zirconium additions canfacilitate in grain size reduction of the metal alloy, improve ductilityof the metal alloy and/or increases the yield strength of the metalalloy. The process of the present invention is used to form a solid orhomogeneous solution of metal alloy that results in a metal alloy havingthe desired tensile yield strength and ultimate tensile strength of themetal alloy. Nitrogen in the metal alloy is an interstitial element thatraises the Ductile Brittle Transition Temperature (DBTT). When the DBTTis too high, the metal alloy can become brittle. The maintenance ofnitrogen below about 20 ppm overcomes this brittleness problem. Theprecess of the present invention can be used to control the nitrogencontent of the metal alloy during the forming and working of the metalalloy. The combination of the various properties of the solid orhomogeneous solution of the metal alloy enables the metal alloy to beformed into a metal device such as a stent, which such a stent hassuperior performance characteristics such as, but not limited tom highradiopacity with thinner and narrower struts and simultaneously having aradial force adequate to retain the vessel lumen fairly open and preventany recoil. The metal alloy can be fabricated from a tubing with anouter diameter as small as about 0.070 inch and with a wall thickness assmall as about 0.002 inch in accordance with the precess of the presentinvention. In one particular design, the average wall thickness of thetubing after the final processing of the metal alloy tube in accordancewith the process of the present invention is about 0.0021-0.00362 inch,and the average concentricity deviation after the final processing ofthe alloy tube is about 1-20%. As can be appreciated, the size values ofthe processed metal alloy set forth above are merely exemplary for usingthe metal alloy to form a metal device such as a stent. For instance,when the metal alloy is used to form other types of stents for use indifferent regions of a body, the size values of the final processedmetal alloy can be different. The solid or homogeneous solution of themetal alloy has the unique characteristics of purity, ductility, grainsize, tensile elongation, yield strength and ultimate tensile strengththat permits the metal alloy to be fabricated into tubing withoutcreating microcracks that are detrimental to the properties of varioustypes of medical devices (e.g. stent, etc.).

Referring again to FIG. 1, the stent is an expandable stent that can beused to at least partially expanding occluded segments of a bodypassageway; however, the stent can have other or additional uses. Forexample, the expandable stent can be used as, but not limited to, 1) asupportive stent placement within a blocked vasculature opened bytransluminal recanalization, which are likely to collapse in the absenceof an internal support; 2) forming a catheter passage throughmediastinal and/or other veins occluded by inoperable cancers; 3)reinforcing a catheter creating intrahepatic communication betweenportal and/or hepatic veins in patients suffering from portalhypertension; 4) a supportive stent placement of narrowing of theesophagus, the intestine, the ureter and/or the urethra; and/or 5) asupportive stent reinforcement of reopened and previously obstructedbile ducts. Accordingly, use of the term “stent” encompasses theforegoing or other usages within various types of body passageways, andalso encompasses use for expanding a body passageway. The stent can beimplanted or applied in a body passageway by techniques such as, but notlimited to, balloon delivery, sheath catheter delivery, etc.

As shown in FIG. 1, the stent 20 includes at least one body member 30having a first end 32, a second end 34, and member structures 36disposed between the first and second ends. The body member is typicallytubular shaped; however, it can be appreciated that the stent can have avariety of shapes and/or configurations. As can also be appreciated, thestent can be formed of one body member of a plurality of body membersthat are connected together. Body member 30 has a first diameter whichpermits delivery of the body member into a body passageway. The firstdiameter of the body member is illustrated as substantially constantalong the longitudinal length of the body member. As can be appreciated,the body member can have a varying first diameter along at least aportion of the longitudinal length of the body member. The body memberalso has a second expanded diameter, not shown. The second diametertypically varies in size; however, the second diameter can benon-variable. The stent can be expanded in a variety of ways such as bya balloon or be self expanding. A balloon expandable stent is typicallypre-mounted or crimped onto an angioplasty balloon catheter. The ballooncatheter is then positioned into the patient via a guide wire. Once thestent is properly positioned, the balloon catheter is inflated to theappropriate pressure for stent expansion. After the stent has beenexpanded, the balloon catheter is deflated and withdrawn, leaving thestent deployed at the treatment site. The metal alloy that is used to atleast partially form the stent has very little recoil, thus once thestent is expanded, the stent substantially retains its expanded shape.

One or more surfaces of the stent can be treated so as to have generallysmooth surfaces. Generally, the ends are treated by filing, buffing,polishing, grinding, coating, and/or the like; however, this is notrequired. As a result, sharp edges, pointed surfaces and the like aresubstantially eliminated from the end section of the stent. Typicallymost, if not all, the ends of the stent are treated to have smoothsurfaces. The smooth surfaces of the ends reduce damage to surroundingtissue as the stent is positioned in and/or expanded in a bodypassageway. One or more portions of the stent can include one or morebiological agents.

The stent can include one or more coating and/or one or more surfacestructures and/or micro-structures. The one or more surface structuresand/or micro-structures can be formed by a variety of processes (e.g.,machining, chemical modifications, chemical reactions, MEMS (e.g.,micro-machining, etc.), etching, laser cutting, etc.). The one or morecoatings and/or one or more surface structures and/or micro-structuresof the stent can be used for a variety of purposes such as, but notlimited to, 1) increasing the bonding and/or adhesion of one or moreagents, adhesives, marker materials and/or polymers to the stent, 2)changing the appearance or surface characteristics of the stent, and/or3) controlling the release rate of one or more agents.

The metal alloy that forms the body of the stent can be coated with oneor more agents or polymers that can be used to improve the functionalityor success of the stent. The one or more polymer coatings can be porousor non-porous polymers. Non-limiting examples of the one or morepolymers that can be coated on one or more regions of the metal alloyinclude, but are not limited to, parylene, a parylene derivative,chitosan, a chitosan derivative, PLGA, a PLGA derivative, PLA, a PLAderivative, PEVA, a PEVA derivative, PBMA, a PBMA derivative, POE, a POEderivative, PGA, a PGA derivative, PLLA, a PLLA derivative, PAA, a PAAderivative, PEG, a PEG derivative, or combinations thereof. The one ormore agents can include, but are not limited to, anti-biotic agents,anti-body targeted therapy agents, anti-hypertensive agents,anti-microbial agents, anti-mitotic agents, anti-oxidants,anti-polymerases agents, anti-proliferative agents, anti-secretoryagents, anti-tumor agents, anti-viral agents, bioactive agents,chemotherapeutic agents, cellular components, cytoskeletal inhibitors,drug, growth factors, growth factor antagonists, hormones,immunosuppressive agents, living cells, non-steroidal anti-inflammatorydrugs, radioactive materials, radio-therapeutic agents, thrombolyticagents, vasodilator agents, etc. Non-limiting examples of agents thatcan be used include a vascular active agent that inhibits and/orprevents restenosis, vascular narrowing and/or in-stent restenosis suchas, but not limited to, trapidil, trapidil derivatives, taxol, taxolderivatives, cytochalasin, cytochalasin derivatives, paclitaxel,paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof As can be appreciated, other oradditional agents can be included on the stent to improve thefunctionality or success of the stent. The amount of agent delivered toa certain region of a patient's body can be controlled by varying thetype of agent, the coating thickness of the agent, the drugconcentration of the agent, the solubility of the agent, the locationthe agent that is coated and/or impregnated on and/in the stent, theamount of surface area of the stent that is coated and/or impregnatedwith the agent, the location of the agent on the stent, etc.

When one or more agents are included on and/or in the stent, the one ormore agents can be controllably released and/or immediately released tooptimize their effects and/or to compliment the function and success ofthe stent. The controlled release can be accomplished by 1) controllingthe size of the surface structures, micro-structures and/or internalstructures in the stent, and/or 2) using one or more polymer coatings;however, other or additional mechanisms can be used to control therelease rate of one or more agents from the stent. The controlledrelease can be accomplished by 1) controlling the size of the surfacestructures, micro-structures and/or internal structures in the stent,and/or 2) using one or more polymer coatings; however, other oradditional mechanisms can be used to control the release rate of one ormore agents from the stent. For example, the amount of agent deliveredto a certain region of a patient's body can be controlled by, but notlimited to, one or more of the following: a) selecting the type of agentto be used on and/or in the stent, b) selecting the amount of agent tobe used on and/or in the stent, c) selecting the coating thickness ofthe agent to be used on the stent, d) selecting the drug concentrationof the agent to be used on and/or in the stent, e) selecting thesolubility of the agent to be used on and/or in the stent, f) selectingthe location the agent that is to be coated and/or impregnated on and/inthe stent, g) selecting the amount of surface area of the stent that iscoated and/or impregnated with the agent, h) selecting the location ofthe agent on the stent, i) selecting the size, shape, amount and/orlocation of the one or more surface structures, micro-structures and/orinternal structures of the stent that include and/or are integrated withthe agent, j) selecting the type and/or amount of polymer to be mixedwith the agent, k) selecting the type, amount and/or coating thicknessof the polymer coating used to at least partially coat and/orencapsulate the agent, etc. The one or more agents can be combined withand/or at least partially coated with a polymer that affects the rate atwhich the biological agent is released from the stent; however, this isnot required. The polymer coating can also or alternatively be used toassist in binding the one or more biological agents to the stent;however, this is not required. The polymer coating, when used, can bebiodegradable or biostable. The polymer coating can be formulated toform a bond with the biological agent to the stent; however, this is notrequired. The one or more polymers used in the polymer coating and theone or more biological agents can be mixed together prior to beingapplied to the stent; however, this is not required. The one or morebiological agents that are used in combination with a one or morepolymers in the polymer coating can control the release of thebiological agent by molecular diffusion; however, this is not required.The thickness of the polymer coating can be about 0.5-25μ; however,other coating thickness can be used. The time period the one or morebiological agents are released from the stent can vary. The one or morebiological agents, when used, can be coated on the surface of the metalalloy, on the surface of one or more polymer layers, and/or mixed withone or more polymer layers. One or more biological agents can also becoated on the top surface of stent 20. At least one biological agent canbe entrapped within and/or coated over with a non-porous polymer layerto at least partially control the release rate of the biological rate;however, this is not required. When a non-porous polymer layer is usedon the stent, the non-porous polymer typically includes parylene C,parylene N, parylene F and/or a parylene derivative; however, other oradditional polymers can be used. Various coating combinations can beused on the stent. For instance, a polymer layer that includes one ormore polymers can be coated on the top of the layer of one or morebiological agents; however, this is not required. In another example,the metal alloy 40 can includes a layer of one or more polymers. A layerof one or more biological agent can be coated on the top of the layer ofone or more polymers; however, this is not required. Furthermore, one ormore polymers can be coated on the layer of one or more biologicalagents; however, this is not required. As can be appreciated othercoating combinations can be used. Generally, one or more biologicalagent are released from the stent for at least several days after thestent is inserted in the body of a patient; however, this is notrequired. Generally, one or more biological agents are released from thestent for at least about 1-7 days after the stent is inserted in thebody of a patient, typically at least about 1-14 days after the stent isinserted in the body of a patient, and more typically about 1-365 daysafter the stent is inserted in the body of a patient; however, this isnot required. As can be appreciated, the time frame that one or more ofthe biological agents are released from the stent can be shorter orlonger. The one or more biological agents that are released from thestent can be controllably released and/or non-controllably released. Thetime period for the release of two or more biological agents from thestent can be the same or different. The type of the one or morebiological agents used on the stent, the release rate of the one or morebiological agents from the stent, and/or the concentration of the one ormore biological agents being released from the stent during a certaintime period is typically selected to deliver the one or more biologicalagents to the area of treatment and/or disease. When the stent is usedin the vascular system, the one or more biological agent can be used toinhibit or prevent thrombosis, restenosis, vascular narrowing and/orin-stent restenosis after the stent has been implanted; however, this isnot required. When the stent is use in the vascular system, thebiological agent that is generally included on and/or in the stent is,but not limited to, trapidil, trapidil derivatives, taxol, taxolderivatives, cytochalasin, cytochalasin derivatives, paclitaxel,paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof; however, it will be appreciatedthat other or additional biological agents can be used. In addition,many other or additional biological agents can be included on and/or inthe stent such as, but not limited to, the following categories ofbiological agents: thrombolytics, vasodilators, anti-hypertensiveagents, anti-microbial or anti-biotic, anti-mitotic, anti-proliferative,anti-secretory agents, non-steroidal anti-inflammatory drugs,immunosuppressive agents, growth factors and growth factor antagonists,chemotherapeutic agents, anti-polymerases, anti-viral agents, anti-bodytargeted therapy agents, hormones, anti-oxidants, radio-therapeuticagents, radiopaque agents and/or radio-labeled agents.

The surface of the metal alloy can be treated to enhance the coating ofthe stent and/or to enhance the mechanical characteristics of the stent;however, this is not required. Such surface treatment techniquesinclude, but are not limited to, cleaning, buffing, smoothing, etching(chemical etching, plasma etching, etc.), etc. When an etching processis used, various gasses can be used for such a surface treatment processsuch as, but not limited to, carbon dioxide, nitrogen, oxygen, Freon,helium, hydrogen, etc. The plasma etching process can be used to cleanthe surface of the stent, change the surface properties of the stent soas to affect the adhesion properties, lubricity properties, etc. of thesurface of the stent. As can be appreciated, other or additional surfacetreatment processes can be used prior to the coating of one or morebiological agents and/or polymers on the surface of the stent.

Various coating combinations can be used on the stent. For example, thebase structure of the stent can include a layer of biological agentand/or polymer. The layer of biological agent and/or polymer can includeone or more biological agents and/or polymers. In one non-limitingexample, the layer can include trapidil, trapidil derivatives, taxol,taxol derivatives, cytochalasin, cytochalasin derivatives, paclitaxel,paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, and combinations thereof. The layer can also oralternatively include one or more polymers. The polymer can include oneor more porous polymers and/or non-porous polymers, and/or biostableand/or biodegradable polymers. When the stent includes and/or is coatedwith one or more polymers, such polymers can include, but are notlimited to, parylene, parylene C, parylene N, parylene F, PLGA, PEVA,PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/or derivatives of oneor more of these polymers. The polymer, when including one or morenon-porous polymers, can at least partially controls a rate of releaseby molecular diffusion of the one or more biological agents; however,this is not required. The one or more non-porous polymers can include,but are not limited to, parylene C, parylene N, parylene F and/or aparylene derivative.

The stent can include one or more needles or micro-needles formed on thesurface of the metal alloy. These needles or micro-needles can be formedby MEMS (e.g., micro-machining, etc.) technology and/or by otherprocesses. The needles or micro-needles can have a variety of shapes andsizes. The needles or micro-needles can be at least partially formedfrom one or more polymers and/or biological agents. It can beappreciated that the needles or micro-needles can be at least partiallyformed of other of additional material such as, but not limited to oneor more adhesives, etc. For instance, the needles or micro-needles caninclude a combination of one or more polymers and/or one or morebiological agents. As can be appreciated, one or more layer of one ormore biological agents and/or polymers can be coated on the needles ormicro-needles; however, this is not required. When the one or moreneedles or micro-needles include and/or are coated with one or morebiological agents, such biological agents can include, but are notlimited to, trapidil, trapidil derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof; however other or additional biological agents canbe used. The use of one or more biological agents to coat the topsurface of the needles or micro-needles can provide a burst ofbiological agent in the interior of the blood vessel and/or the bloodvessel itself during and/or after insertion of the stent. The polymerthat is used to at least partially form the needles or micro-needlesand/or is coated on the needles or micro-needles can be porous,non-porous, biodegradable and/or biostable. Polymers that can be used toat least partially form the one or more needles or micro-needlesinclude, but are not limited to, Non-limiting examples of one or morepolymers that can be used include, but are not limited to, parylene,parylene C, parylene N, parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA,PLLA, PAA, PEG, chitosan and/or derivatives of one or more of thesepolymers; however, other or additional polymers can be used. The polymercoating, when used, can be used to 1) provide protection to thestructure of the one or more needles or micro-needles, 2) at leastpartially control a rate of degradation of the one or more needles ormicro-needles, and/or 3) at least partially control a rate of release ofone or more biological agents on and/or in the one or more needles ormicro-needles. As can be appreciated, polymer coating can have other oradditional functions. The outer surface of the needles or micro-needlescan include one or more layers of one or more biological agents toprovide a burst of biological agent in the interior of a body passagewayand/or in the body passageway itself during and/or after insertion ofthe stent; however, this is not required. The one or more biologicalagents that can be used can include, but are not limited to, trapidil,trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof, andcombinations thereof; however other or additional biological agents canbe used.

The metal alloy used to form the stent can include one or more surfacestructures or micro-structures in the form of a mound; however, it canbe appreciated that other or additional shapes can be used. The mound isformed on the surface of the metal alloy. The mound can be formed byMEMS (e.g., micro-machining, etc.) technology and/or by other processes.The mound is shown to be formed of one or more biological agents;however, it can be appreciated that the mound can be formed of one ormore polymers or a combination of one or more polymers and biologicalagents. As can also be appreciated, other or additional materials can beused to at least partially form the mound. The one or more biologicalagents can include, but are not limited to, trapidil, trapidilderivatives, 5-Phenylmethimazole, 5-Phenylmethimazole derivatives,GM-CSF, GM-CSF derivatives, or combinations thereof; however other oradditional biological agents can be used. The one or more biologicalagents used to form the mound can provide a burst of biological agent inthe interior of a body passageway and/or the body passageway itselfduring and/or after insertion of the stent in the body passageway;however, this is not required. As can be appreciated, a layer of one ormore polymers can be coated on the mound; however, this is not required.The polymer layer can be used to control the release rate of the one ormore biological agents from the mound; however, this is not required.The polymer layer can also or alternatively provide protection to themound structure; however, this is not required. When the mound includesand/or is coated with one or more polymers, such polymers can include,but are not limited to, parylene, parylene C, parylene N, parylene F,PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/orderivatives of one or more of these polymers. One or more internalchannels can be formed in one or more needles or micro-needles; however,this is not required. The one or more internal channels can include oneor more biological agent and/or polymers.

The invention has been specifically described with respect to theformation of a stent. As can be appreciated, other types of medicaldevices can be formed by use of one or more of the novel processing stepof the present invention. For example, the novel metal allow can bedrawn using one or more of the processes of the present invention toform a thin wire for use as a suture, a guide wire, a stent, or thelike.

It will thus be seen that the objects set forth above, among those madeapparent from the preceding description, are efficiently attained, andsince certain changes may be made in the constructions set forth withoutdeparting from the spirit and scope of the invention, it is intendedthat all matter contained in the above description and shown in theaccompanying drawings shall be interpreted as illustrative and not in alimiting sense. The invention has been described with reference topreferred and alternate embodiments. Modifications and alterations willbecome apparent to those skilled in the art upon reading andunderstanding the detailed discussion of the invention provided herein.This invention is intended to include all such modifications andalterations insofar as they come within the scope of the presentinvention. It is also to be understood that the following claims areintended to cover all of the generic and specific features of theinvention herein described and all statements of the scope of theinvention, which, as a matter of language, might be said to falltherebetween.

1-26. (canceled)
 27. A method for forming a medical device comprisingthe steps of: a) forming a rod or tube having a surface and an outercross-sectional area, said rod or tube including a metal alloy that isformed of at least about 95 weight percent of a solid solution ofmolybdenum and rhenium or tungsten and tantalum; b) drawing down saidouter cross-sectional area of said rod or tube by a reducing mechanism;c) annealing said rod or tube at an annealing temperature in an oxygenreducing environment or inert environment after said rod or tube hasbeen drawn down; d) cooling said annealed rod or tube at a rate of atleast about 100° C. per minute; e) drawing down said cross-sectionalarea of said rod or tube by the reducing mechanism after said rod ortube has been annealed; and, f) annealing said rod or tube at least oneadditional time at an annealing temperature that is lower temperaturethan at least one annealing temperature of a previous annealing of saidrod or tube.
 28. The method as defined in claim 27, wherein said step offorming said rod or tube includes a process of isostatically pressingmetal powder together and subsequently sintering said metal power toform said rod or tube in a controlled atmosphere, said rod or tubehaving an average density of about 0.7-0.95 a minimum theoreticaldensity of said metal alloy, said rod or tube have an average density ofabout 12-14 gm/cc, said controlled atmosphere including an inertatmosphere, an oxygen reducing atmosphere, or a vacuum.
 29. The methodas defined in claim 28, wherein said tube is formed by gun drilling, EDMcutting, or combinations thereof a passageway at least partially througha longitudinal length of said rod.
 30. The method as defined in claim27, wherein said step of forming said rod or tube includes a) forming aningot of metal, b) extruding said ingot through a die to form a rod, c)hollowing out said rod to form a passageway at least partially through alongitudinal length of said rod, and d) polishing a surface of saidpassageway.
 31. The method as defined in claim 30, wherein said step ofhollowing includes gun drilling, EDM cutting, or combinations thereofsaid rod to form said passageway.
 32. The method as defined in claim 1,wherein said metal alloy includes about 41-49 weight percent rhenium,about 51-59 weight percent molybdenum, and up to about 1 weight percentadditional metal, said additional metal including a metal selected fromthe group consisting of titanium, yttrium, zirconium, or mixturesthereof
 33. The method as defined in claim 27, including the step ofnitriding said rod or tube to form a nitride layer on said rod or tubeprior to at least one drawing down step, said step of nitridingincluding a) exposing at least a portion of said rod or tube to anitriding gas that includes nitrogen, nitrogen and hydrogen, orcombinations thereof, and b) exposing at least a portion of said rod ortube to a nitriding gas at a temperature of less than about 400° C. forat least about 1 minute.
 34. The method as defined in claim 33,including the step of removing said nitride layer on said rod or tubeprior to annealing said rod or tube.
 36. The method as defined in claim27, including the step of protecting said rod or tube from oxygen whensaid rod or tube is exposed to temperatures of greater than about400-500° C.
 37. The method as defined in claim 27, wherein said step ofdrawing down said cross-sectional area of said rod or tube by a reducingmechanism that reduces said cross-sectional area by less than about 20%each time said rod or tube is processed by said reducing mechanism. 38.The method as defined in claim 37, wherein said step of drawing downincludes the step of inserting a close-fitting rod in said passageway ofsaid tube prior to using said reducing mechanism on said tube.
 39. Themethod as defined in claim 27, wherein said step of annealing said rodor tube includes the steps of a) annealing the rod or tube at anannealing temperature of at least about 1480° C. for a time period of atleast about 5 minutes for a time period of at least about 5 minutes whensaid rod or tube has wall thickness of greater than about 0.015 inch, b)annealing the rod or tube at an annealing temperature of about1450-1480° C. for a time period of at least about 5 minutes when saidrod or tube has wall thickness of about 0.008-0.015 inch, and c)annealing the rod or tube at an annealing temperature of less than about1450° C. for a time period of at least about 5 minutes when said rod ortube has wall thickness of less than about 0.008 inch.
 40. The method asdefined in claim 27, wherein said medical device is a stent.
 41. Themethod as defined in claim 27, where said rod or tube after completionof all of the annealing steps has an average grain size of 4-14 ASTM.42. The method as defined in claim 27, wherein one or more portions ofthe rod or tube includes smaller tubular structures or segments affixedto each other, each of said tubular structures or segments can beannealed prior to and/or after separation from the initial rod or tube,secondary forming, being affixed to additional segments to construct thetubular device, secondary pickle and/or electropolish processes, orcombinations thereof.
 43. The method as defined in claim 27, whereinsaid initial tube has a wall thickness of about 0.001-0.100 inch.
 44. Amethod for forming a stent comprising the steps of: a) forming a tubehaving a surface and an outer cross-sectional area, said tube formed ofa metal alloy comprising about 41-49 weight percent rhenium, about 51-59weight percent molybdenum; b) drawing down said outer cross-sectionalarea of said tube by a reducing mechanism; c) nitriding said tube toform a nitride layer on said tube prior to at least one of said drawingdown steps, said step of nitriding including i) exposing at least aportion of said tube to a nitriding gas that includes nitrogen, nitrogenand hydrogen, or combinations thereof, and b) exposing at least aportion of said tube to a nitriding gas at a temperature of less thanabout 400° C. for at least about 1 minute, said nitride layer removedprior to said tube being annealed; d) annealing said tube at anannealing temperature in an oxygen reducing environment or inertenvironment after said tube has been drawn down; e) cooling saidannealed tube at a rate of at least about 100° C. per minute; f) drawingdown said cross-sectional area of said tube by the reducing mechanismafter said rod or tube has been annealed, said step of drawing down saidcross-sectional area of said tube reduces said cross-sectional area byless than about 20% each time said tube is processed by said reducingmechanism; g) annealing said rod or tube at least one additional time atan annealing temperature that is lower temperature than at least oneannealing temperature of a previous annealing of said rod or tube, saidsteps of annealing said tube include the steps of a) annealing said tubeat an annealing temperature of at least about 1480° C. for a time periodof at least about 5 minutes for a time period of at least about 5minutes when said tube has wall thickness of greater than about 0.015inch, b) annealing said tube at an annealing temperature of about1450-1480° C. for a time period of at least about 5 minutes when saidtube has wall thickness of about 0.008-0.015 inch, and c) annealing saidtube at an annealing temperature of less than about 1450° C. for a timeperiod of at least about 5 minutes when said tube has wall thickness ofless than about 0.008 inch; h) protecting said tube from oxygen whensaid tube is exposed to temperatures of greater than about 400-500° C.;and, i) cutting said tube to form said stent, said stent formed of a cuttube having an average grain size of 4-14 ASTM.
 45. The method asdefined in claim 44, wherein said step of drawing down includes the stepof inserting a close-fitting rod in said passageway of said tube priorto using said reducing mechanism on said tube.